|
1
|
Gideonse BM, Birkeland M, Vilstrup MH, Grupe P, Naghavi-Behzad M, Ruhlmann CH, Gerke O, Hildebrandt MG. Organ-specific accuracy of [ 18F]FDG-PET/CT in identifying immune-related adverse events in patients with high-risk melanoma treated with adjuvant immune checkpoint inhibitor. Jpn J Radiol 2024; 42:753-764. [PMID: 38504000 PMCID: PMC11217074 DOI: 10.1007/s11604-024-01554-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Accepted: 03/01/2024] [Indexed: 03/21/2024]
Abstract
PURPOSE This study aimed to determine the organ-specific accuracy of [18F]FDG-PET/CT in identifying immune-related adverse events (irAEs) in patients with high-risk (stage III/IV) surgically resected melanoma treated with an adjuvant immune checkpoint inhibitor (ICI) and determine the incidence of irAEs within the first year after starting treatment. MATERIALS AND METHODS This registry-based study included individuals who had undergone surgical removal of melanoma and were undergoing adjuvant ICI treatment (either nivolumab or pembrolizumab). The study specifically enrolled patients who had undergone both a baseline and at least one subsequent follow-up [18F]FDG-PET/CT scan. Follow-up scans were performed every third month in the first year after surgery to screen for disease recurrence. We retrospectively compared the follow-up scans with baseline scans to identify irAEs. Clinical information on irAEs was obtained from medical records and served as a reference standard for determining the accuracy of [18F]FDG-PET/CT. RESULTS A total of 123 patients with 363 [18F]FDG-PET/CT scans were included, and 65 patients (52.8%) developed irAEs. In decreasing order, the organ-specific incidences of irAEs were: skin 26/65 (40%), muscle and joints 21/65 (32.3%), intestines 13/65 (20%), thyroid gland 12/65 (18.5%), lungs 4/65 (6.2%), and heart 2/65 (3.1%). The sensitivities and specificities of [18F]FDG-PET/CT for diagnosing irAEs were: skin 19% (95% CI: 7-39%) and 95% (88-98%), muscles and joints 71% (48-89%) and 83% (75-90%), intestines 100% (75-100%) and 85% (77-91%); thyroid gland 92% (62-99%) and 95% (89-98%), lungs 75% (19-99%) and 90% (83-95%), and heart 50% (13-99%) and 97% (92-99%), respectively. CONCLUSION [18F]FDG-PET/CT generally had moderate to high sensitivities (except for skin and heart) and specificities in diagnosing irAEs in patients receiving adjuvant ICI; this could be suggested to be systematically assessed and reported in scan reports.
Collapse
Affiliation(s)
- Birte Molvik Gideonse
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark
| | - Magnus Birkeland
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark
| | - Mie Holm Vilstrup
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark
- Department of Radiology and Nuclear Medicine, Esbjerg Hospital, Esbjerg, Denmark
| | - Peter Grupe
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark
| | - Mohammad Naghavi-Behzad
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
- Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark.
- Centre for Personalized Response Monitoring in Oncology, Odense University Hospital, Odense, Denmark.
| | - Christina H Ruhlmann
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Oncology, Odense University Hospital, Odense, Denmark
| | - Oke Gerke
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark
| | - Malene Grubbe Hildebrandt
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark
- Centre for Personalized Response Monitoring in Oncology, Odense University Hospital, Odense, Denmark
- Centre for Innovative Medical Technology, Odense University Hospital, Odense, Denmark
| |
Collapse
|
|
2
|
Lee H, Hwang KH. Focal incidental colorectal fluorodeoxyglucose uptake: Should it be spotlighted? World J Clin Cases 2024; 12:2466-2474. [PMID: 38817235 PMCID: PMC11135452 DOI: 10.12998/wjcc.v12.i15.2466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 03/17/2024] [Accepted: 04/12/2024] [Indexed: 05/14/2024] Open
Abstract
Fluorine-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography/computed tomography (PET/CT) has emerged as a cornerstone in cancer evaluation imaging, with a well-established history spanning several years. This imaging modality, encompassing the examination of the body from the base of the skull to the upper thighs, comprehensively covers the chest and abdominopelvic regions in a singular scan, allowing for a holistic assessment of nearly the entire body, including areas of marginal interest. The inherent advantage of this expansive scan range lies in its potential to unveil unexpected incidental abnormal hypermetabolic areas. The identification of incidental focal FDG uptake within colorectal regions during PET/CT scans is not an uncommon occurrence, albeit fraught with challenges associated with non-specific FDG uptake. The presence of benign colorectal lesions or physiological uptake poses a particular obstacle, as these may manifest with FDG uptake levels that mimic malignancy. Consequently, physicians are confronted with a diagnostic dilemma when encountering abnormal FDG uptake in unexpected colorectal areas. Existing studies have presented divergent results concerning these uptakes. Standardized uptake value and its derivatives have served as pivotal metrics in quantifying FDG uptake in PET images. In this article, we aim to succinctly explore the distinctive characteristics of FDG, delve into imaging findings, and elucidate the clinical significance of incidental focal colorectal uptake. This discussion aims to contribute valuable insights into the nuanced interpretation of such findings, fostering a comprehensive understanding.
Collapse
Affiliation(s)
- Haejun Lee
- Department of Nuclear Medicine, Gachon University College of Medicine, Gil Medical Center, Incheon 21565, South Korea
| | - Kyung-Hoon Hwang
- Department of Nuclear Medicine, Gachon University College of Medicine, Gil Medical Center, Incheon 21565, South Korea
| |
Collapse
|
|
3
|
Lee H, Hwang KH. Unexpected focal fluorodeoxyglucose uptake in main organs; pass through or pass by? World J Clin Cases 2024; 12:1885-1899. [PMID: 38660550 PMCID: PMC11036514 DOI: 10.12998/wjcc.v12.i11.1885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Revised: 01/31/2024] [Accepted: 03/21/2024] [Indexed: 04/11/2024] Open
Abstract
Since the inception of fluorine-18 fluorodeoxyglucose (F-18 FDG), positron emission tomography/computed tomography (PET/CT) utilizing F-18 FDG has become widely accepted as a valuable imaging modality in the field of oncology, with global prevalence in clinical practice. Given that a single Torso PET/CT scan encompasses the anatomical region from the skull base to the upper thigh, the detection of incidental abnormal focal hypermetabolism in areas of limited clinical interest is both feasible and not uncommon. Numerous investigations have been undertaken to delineate the distinctive features of these findings, yet the outcomes have proven inconclusive. The incongruent results of these studies present a challenge for physicians, leaving them uncertain about the appropriate course of action. This article provides a succinct overview of the characteristics of fluorodeoxyglucose, followed by a comprehensive discussion of the imaging findings and clinical significance associated with incidental focal abnormal F-18 FDG activity in several representative organs. In conclusion, while the prevalence of unrecognized malignancy varies across organs, malignancies account for a substantial proportion, ranging from approximately one-third to over half, of incidental focal uptake. In light of these rates, physicians are urged to exercise vigilance in not disregarding unexpected uptake, facilitating more assured clinical decisions, and advocating for further active evaluation.
Collapse
Affiliation(s)
- Haejun Lee
- Department of Nuclear Medicine, Gachon University College of Medicine, Gil Medical Center, Incheon 21565, South Korea
| | - Kyung-Hoon Hwang
- Department of Nuclear Medicine, Gachon University College of Medicine, Gil Medical Center, Incheon 21565, South Korea
| |
Collapse
|
|
4
|
Ke Z, Lu Z, Li Q, Tong W. Intestinal glucose excretion: A potential mechanism for glycemic control. Metabolism 2024; 152:155743. [PMID: 38007149 DOI: 10.1016/j.metabol.2023.155743] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 11/20/2023] [Accepted: 11/20/2023] [Indexed: 11/27/2023]
Abstract
The gut has been increasingly recognized in recent years as a pivotal organ in the maintenance of glucose homeostasis. Specifically, the profound and enduring improvement in glucose metabolism achieved through metabolic surgery to modify the anatomy of the gut has prompted scholars to acknowledge that the most effective strategy for treating type 2 diabetes mellitus (T2DM) involves the gut. The mechanisms underlying the regulation of glucose metabolism by the gut encompass gut hormones, bile acids, intestinal gluconeogenesis, gut microbiota, and signaling interactions between the gut and other organs (liver, brain, adipose, etc.). Recent studies have also revealed a novel phenomenon of glucose lowering through the gut: metabolic surgery and metformin promote the excretion of glucose from the circulation into the intestinal lumen by enterocytes. However, there is still limited understanding regarding the underlying mechanisms of intestinal glucose excretion and its contribution to glycemic control. This article reviews current research on intestinal glucose excretion while focusing on its role in T2DM management as well as potential mechanisms.
Collapse
Affiliation(s)
- Zhigang Ke
- Department of General Surgery, Daping Hospital, Army Medical University, Chongqing 400042, China
| | - Zongshi Lu
- Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Army Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China
| | - Qing Li
- Department of General Surgery, Daping Hospital, Army Medical University, Chongqing 400042, China
| | - Weidong Tong
- Department of General Surgery, Daping Hospital, Army Medical University, Chongqing 400042, China.
| |
Collapse
|
|
5
|
Lovinfosse P, Hustinx R. The role of PET imaging in inflammatory bowel diseases: state-of-the-art review. THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING : OFFICIAL PUBLICATION OF THE ITALIAN ASSOCIATION OF NUCLEAR MEDICINE (AIMN) [AND] THE INTERNATIONAL ASSOCIATION OF RADIOPHARMACOLOGY (IAR), [AND] SECTION OF THE SOCIETY OF... 2022; 66:206-217. [PMID: 35708600 DOI: 10.23736/s1824-4785.22.03467-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/22/2023]
Abstract
Inflammatory bowel diseases (IBD), i.e. Crohn disease and ulcerative colitis, are autoimmune processes of undetermined origin characterized by the chronic inflammation of the digestive tract. There is no single gold-standard to diagnose IBD which is therefore carried out through the combination of endoscopy, biopsy, radiological and biological investigations; and the development of non-invasive technique allowing the assessment and monitoring of these diseases is necessary. In this state-of-the-art review of the literature, we present the results of PET imaging studies for the diagnosis and staging of IBD (suspected or known), response evaluation to treatment and evaluation of one the main complication, i.e. strictures; explain the reasons why this examination is currently not considered in the IBD guidelines, e.g. radiation exposure, lack of standardization and not validated performances; and finally discuss the perspectives that could possibly allow it to find a place in the future, e.g. digital PET-CT, dynamic PET images acquisition, new radiopharmaceuticals, use of radiomics and use of artificial intelligence for automatically characterize and quantify digestive [18F]FDG uptake.
Collapse
Affiliation(s)
- Pierre Lovinfosse
- Division of Nuclear Medicine and Oncological Imaging, University Hospital CHU of Liège, Liège, Belgium -
- GIGA-CRC in vivo Imaging, University of Liège, Liège, Belgium -
| | - Roland Hustinx
- Division of Nuclear Medicine and Oncological Imaging, University Hospital CHU of Liège, Liège, Belgium
- GIGA-CRC in vivo Imaging, University of Liège, Liège, Belgium
| |
Collapse
|
|
6
|
Urhan E, Temizer E, Karaca Z, Abdulrezzak U, Kara CS, Hacioglu A, Unluhizarci K. The effect of additional acarbose on metformin-associated artificially high 18F-Fluorodeoxyglucose uptake in positron emission tomography/computed tomography. Acta Diabetol 2022; 59:929-937. [PMID: 35429263 DOI: 10.1007/s00592-022-01890-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 04/04/2022] [Indexed: 11/01/2022]
Abstract
AIM Metformin causes diffuse and intense fluorodeoxyglucose (FDG) uptake more frequently in the colon and less frequently in the small intestine. In this study, we aimed to investigate the effect of simultaneous use of acarbose and metformin on FDG uptake in positron emission tomography/computed tomography (PET/CT), which has not been investigated previously. METHODS Totally 145 patients with a median age of 65 years (range: 18-80 years), who underwent FDG PET/CT in the Department of Nuclear Medicine of Erciyes University Medical School between 2018 and 2021, were involved in the study. The patients undergoing PET/CT were categorized as metformin plus acarbose users (group MA), metformin users (group M), and control subjects without diabetes (group C). The maximum and mean standard uptake values (SUVmax and SUVmean) of FDG uptake of the all intestine segments were measured separately. RESULTS The number of participants in each group was 35, 51 and 59 in group MA, group M and group C, respectively. The FDG uptake of all intestine was significantly higher in group MA and group M than in group C. The FDG uptake of ascending, transverse, descending, and sigmoid colon was significantly lower in group MA than in group M. The FDG uptake of the small intestine was not different between group MA and group M. The FDG uptake of the rectum was lower in group MA than group M and it was significant for SUVmean, but not significant for SUVmax. CONCLUSION The addition of acarbose to metformin therapy decreased SUV and artificially high FDG uptake in the colon and may be an alternative recommendation to discontinuing metformin in patients going to PET/CT imaging.
Collapse
Affiliation(s)
- Emre Urhan
- Department of Endocrinology, Erciyes University Medical School, Kayseri, Turkey
| | - Emre Temizer
- Department of Nuclear Medicine, Erciyes University Medical School, Kayseri, Turkey
| | - Zuleyha Karaca
- Department of Endocrinology, Erciyes University Medical School, Kayseri, Turkey
| | - Ummuhan Abdulrezzak
- Department of Nuclear Medicine, Erciyes University Medical School, Kayseri, Turkey
| | - Canan Sehit Kara
- Department of Endocrinology, Erciyes University Medical School, Kayseri, Turkey
| | - Aysa Hacioglu
- Department of Endocrinology, Erciyes University Medical School, Kayseri, Turkey
| | - Kursad Unluhizarci
- Department of Endocrinology, Erciyes University Medical School, Kayseri, Turkey.
| |
Collapse
|
|
7
|
Zhang X, Ogihara T, Zhu M, Gantumur D, Li Y, Mizoi K, Kamioka H, Tsushima Y. Effect of metformin on 18F-fluorodeoxyglucose uptake and positron emission tomographic imaging. Br J Radiol 2022; 95:20200810. [PMID: 34705528 PMCID: PMC8822544 DOI: 10.1259/bjr.20200810] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
Metformin is widely used to treat diabetes, but induces changes in glucose uptake in both normal organs and tumors. Here, we review the effects of metformin on the uptake of 18F-fludeoxyglucose (18F-FDG) in tissues and tumors, and its influence on 18F-FDG positron emission tomographic imaging (18F-FDG PET), as well as the mechanisms involved. This is an important issue, because metformin has diverse effects on tissue uptake of 18F-FDG, and this can affect the quality and interpretation of PET images. Metformin increases glucose uptake in the gastrointestinal tract, cerebral white matter, and the kidney, while regions of the cerebrum associated with memory show decreased glucose uptake, and the myocardium shows no change. Hepatocellular carcinoma and breast cancer show increased glucose uptake after metformin administration, while thyroid cancer shows decreased uptake, and colon and pancreatic cancers show no change. A high-energy diet increases 18F-FDG uptake, but this effect is blocked by metformin. Withdrawal of metformin 48 h before PET image acquisition is widely recommended. However, based on our review of the literature, we propose that the differentiation of metformin discontinuation could be reasonable. But future clinical trials are still needed to support our viewpoint.
Collapse
Affiliation(s)
| | | | - Min Zhu
- Weifang Community Health Service Center, Pudong New District, Shanghai, China
| | - Dolgormaa Gantumur
- Department of Hepatobiliary and Pancreatic Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
| | - Yang Li
- Gunma University Heavy Ion Medical Center, Maebashi, Gunma, Japan
| | - Kenta Mizoi
- Laboratory of Biopharmaceutics, Department of Pharmacology, Faculty of Pharmacy, Takasaki University of Health and Welfare, Takasaki, Gunma, Japan
| | | | | |
Collapse
|
|
8
|
Patient preparation for PET studies. Nucl Med Mol Imaging 2022. [DOI: 10.1016/b978-0-12-822960-6.00043-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
|
|
9
|
|
|
10
|
Moasses-Ghafari B, Fallahi B, Esfehani AF, Eftekhari M, Rahmani K, Eftekhari A, Geramifar P. Effect of Diet on Physiologic Bowel 18F-FDG Uptake. J Nucl Med Technol 2021; 49:241-245. [PMID: 34244224 DOI: 10.2967/jnmt.120.257857] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 03/26/2021] [Indexed: 12/30/2022] Open
Abstract
Intestinal 18F-FDG uptake is variable in whole-body PET/CT. In cancer patients, particularly those suspected of relapse or metastasis, 18F-FDG absorption might interfere with scan interpretation. This study evaluated the effect of diet on intestinal 18F-FDG absorption. Methods: In total, 214 patients referring for oncologic 18F-FDG PET/CT participated. They were randomly divided into 2 groups and asked to follow either a routine diet (RD) or a low-carbohydrate, high-fat diet (LCHFD) for 24 h before the study. The small bowel and different parts of the colon (the cecum; the ascending, transverse, and descending segments; and the hepatic and splenic flexures) were evaluated and visually interpreted by nuclear medicine experts. Bowel uptake was graded through comparison with that in the liver as absent, mild, moderate, or severe. Results: Significantly higher 18F-FDG uptake in the descending colon (P = 0.001) and small intestine (P = 0.01) was observed in the RD group than in the LCHFD group. After patients with bowel cancer were omitted from the statistical analysis, no significant differences in the final results were seen. Conclusion: An LCHFD for 24 h before 18F-FDG PET imaging resulted in lower 18F-FDG uptake in the descending colon and small bowel than did an RD, assisting the interpreting physician by reducing the intestinal activity interference for more accurate diagnostic interpretation.
Collapse
Affiliation(s)
| | - Babak Fallahi
- Research Center for Nuclear Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Armaghan Fard Esfehani
- Research Center for Nuclear Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Eftekhari
- Research Center for Nuclear Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Khaled Rahmani
- Social Determinants of Health Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran; and
| | - Arash Eftekhari
- Diagnostic Radiology/Nuclear Medicine, Surrey Memorial Hospital and Jim Pattison Outpatient Care and Surgery Centre, Surrey, British Columbia, Canada
| | - Parham Geramifar
- Research Center for Nuclear Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran;
| |
Collapse
|
|
11
|
Sachpekidis C, Kopp-Schneider A, Pan L, Papamichail D, Haberkorn U, Hassel JC, Dimitrakopoulou-Strauss A. Interim [ 18F]FDG PET/CT can predict response to anti-PD-1 treatment in metastatic melanoma. Eur J Nucl Med Mol Imaging 2021; 48:1932-1943. [PMID: 33336264 PMCID: PMC8113306 DOI: 10.1007/s00259-020-05137-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Accepted: 11/24/2020] [Indexed: 12/11/2022]
Abstract
PURPOSE In an attempt to identify biomarkers that can reliably predict long-term outcomes to immunotherapy in metastatic melanoma, we investigated the prognostic role of [18F]FDG PET/CT, performed at baseline and early during the course of anti-PD-1 treatment. METHODS Twenty-five patients with stage IV melanoma, scheduled for treatment with PD-1 inhibitors, were enrolled in the study (pembrolizumab, n = 8 patients; nivolumab, n = 4 patients; nivolumab/ipilimumab, 13 patients). [18F]FDG PET/CT was performed before the start of treatment (baseline PET/CT) and after the initial two cycles of PD-1 blockade administration (interim PET/CT). Seventeen patients underwent also a third PET/CT scan after administration of four cycles of treatment. Evaluation of patients' response by means of PET/CT was performed after application of the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria and the PET Response Evaluation Criteria for IMmunoTherapy (PERCIMT). Response to treatment was classified into 4 categories: complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD). Patients were further grouped into two groups: those demonstrating metabolic benefit (MB), including patients with SMD, PMR, and CMR, and those demonstrating no MB (no-MB), including patients with PMD. Moreover, patterns of [18F]FDG uptake suggestive of radiologic immune-related adverse events (irAEs) were documented. Progression-free survival (PFS) was measured from the date of interim PET/CT until disease progression or death from any cause. RESULTS Median follow-up from interim PET/CT was 24.2 months (19.3-41.7 months). According to the EORTC criteria, 14 patients showed MB (1 CMR, 6 PMR, and 7 SMD), while 11 patients showed no-MB (PMD). Respectively, the application of the PERCIMT criteria revealed that 19 patients had MB (1 CMR, 6 PMR, and 12 SMD), and 6 of them had no-MB (PMD). With regard to PFS, no significant difference was observed between patients with MB and no-MB on interim PET/CT according to the EORTC criteria (p = 0.088). In contrary, according to the PERCIMT criteria, patients demonstrating MB had a significantly longer PFS than those showing no-MB (p = 0.045). The emergence of radiologic irAEs (n = 11 patients) was not associated with a significant survival benefit. Regarding the sub-cohort undergoing also a third PET/CT, 14/17 patients (82%) showed concordant responses and 3/17 (18%) had a mismatch of response assessment between interim and late PET/CT. CONCLUSION PET/CT-based response of metastatic melanoma to PD-1 blockade after application of the recently proposed PERCIMT criteria is significantly correlated with PFS. This highlights the potential ability of [18F]FDG PET/CT for early stratification of response to anti-PD-1 agents, a finding with possible significant clinical and financial implications. Further studies including larger numbers of patients are necessary to validate these results.
Collapse
Affiliation(s)
- Christos Sachpekidis
- Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69210, Heidelberg, Germany.
| | | | - Leyun Pan
- Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69210, Heidelberg, Germany
| | - Dimitrios Papamichail
- Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69210, Heidelberg, Germany
| | - Uwe Haberkorn
- Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69210, Heidelberg, Germany
- Department of Nuclear Medicine, University of Heidelberg, Heidelberg, Germany
| | - Jessica C Hassel
- Department of Dermatology and National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany
| | - Antonia Dimitrakopoulou-Strauss
- Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69210, Heidelberg, Germany
| |
Collapse
|
|
12
|
Vali R, Alessio A, Balza R, Borgwardt L, Bar-Sever Z, Czachowski M, Jehanno N, Kurch L, Pandit-Taskar N, Parisi M, Piccardo A, Seghers V, Shulkin BL, Zucchetta P, Lim R. SNMMI Procedure Standard/EANM Practice Guideline on Pediatric 18F-FDG PET/CT for Oncology 1.0. J Nucl Med 2021; 62:99-110. [PMID: 33334912 PMCID: PMC8679588 DOI: 10.2967/jnumed.120.254110] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Accepted: 07/21/2020] [Indexed: 02/06/2023] Open
Abstract
The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote the science, technology, and practical application of nuclear medicine. The European Association of Nuclear Medicine (EANM) is a professional nonprofit medical association founded in 1985 to facilitate communication worldwide among individuals pursuing clinical and academic excellence in nuclear medicine. SNMMI and EANM members are physicians, technologists, and scientists specializing in the research and practice of nuclear medicine. The SNMMI and EANM will periodically put forth new standards/guidelines for nuclear medicine practice to help advance the science of nuclear medicine and improve service to patients. Existing standards/guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated. Each standard/guideline, representing a policy statement by the SNMMI/EANM, has undergone a thorough consensus process, entailing extensive review. The SNMMI and EANM recognize that the safe and effective use of diagnostic nuclear medicine imaging requires particular training and skills, as described in each document. These standards/guidelines are educational tools designed to assist practitioners in providing appropriate and effective nuclear medicine care for patients. These guidelines are consensus documents, and are not inflexible rules or requirements of practice. They are not intended, nor should they be used, to establish a legal standard of care. For these reasons and those set forth below, the SNMMI and the EANM cautions against the use of these standards/guidelines in litigation in which the clinical decisions of a practitioner are called into question. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals taking into account the unique circumstances of each case. Thus, there is no implication that action differing from what is laid out in the standards/guidelines, standing alone, is below standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the standards/guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology subsequent to publication of the standards/guidelines. The practice of medicine involves not only the science, but also the art of dealing with the prevention, diagnosis, alleviation, and treatment of disease. The variety and complexity of human conditions make it impossible for general guidelines to consistently allow for an accurate diagnosis to be reached or a particular treatment response to be predicted. Therefore, it should be recognized that adherence to these standards/guidelines will not ensure a successful outcome. All that should be expected is that the practitioner follows a reasonable course of action, based on their level of training, the current knowledge, the available resources, and the needs/context of the particular patient being treated. PET and computerized tomography (CT) have been widely used in oncology. 18F-FDG is the most common radiotracer used for PET imaging. The purpose of this document is to provide imaging specialists and clinicians guidelines for recommending, performing, and interpreting 18F-FDG PET/CT in pediatric patients in oncology. There is not a high level of evidence for all recommendations suggested in this paper. These recommendations represent the expert opinions of experienced leaders in this field. Further studies are needed to have evidence-based recommendations for the application of 18F-FDG PET/CT in pediatric oncology. These recommendations should be viewed in the context of good practice of nuclear medicine and are not intended to be a substitute for national and international legal or regulatory provisions.
Collapse
Affiliation(s)
- Reza Vali
- Department of Diagnostic Imaging, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Adam Alessio
- Michigan State University, East Lansing, Michigan
| | - Rene Balza
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Lise Borgwardt
- Department for Clinical Physiology, Nuclear Medicine & PET, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Zvi Bar-Sever
- Schneider Children's Medical Center, Petach Tikva, Israel
| | | | - Nina Jehanno
- Department of Nuclear Medicine, Institut Curie, Paris, France
| | - Lars Kurch
- University Hospital Leipzig, Department of Nuclear Medicine, Leipzig, Germany
| | | | - Marguerite Parisi
- University of Washington School of Medicine and Seattle Children's Hospital, Seattle, Washington
| | | | - Victor Seghers
- Texas Children's Hospital, Baylor College of Medicine, Houston, Texas
| | - Barry L Shulkin
- St. Jude Children's Research Hospital, Memphis, Tennessee; and
| | | | - Ruth Lim
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| |
Collapse
|
|
13
|
Abstract
FDG-PET/CT has potential in inflammatory bowel disease. The literature generally presents good sensitivity and specificity in various settings. At present, the most promising roles are assessment of early treatment response and stricture characterization, whereas general use in the initial diagnostic workup should be reserved for equivocal cases for the time being. However, it is challenging to image the moving and physiologically active bowel with FDG, and available literature is far from ideal. Thus, several issues remain unclarified, and further data are needed to make firm conclusions on the role of FDG and PET/CT in inflammatory bowel disease.
Collapse
Affiliation(s)
- Jacob Broder Brodersen
- Department of Gastroenterology, Hospital of Southwest Jutland, Finsensgade 35, Esbjerg Dk-6700, Denmark
| | - Søren Hess
- Department of Radiology and Nuclear Medicine, Hospital of Southwest Jutland, Finsensgade 35, Esbjerg Dk-6700, Denmark; Department of Regional Health Research, University of Southern Denmark, Odense, Denmark.
| |
Collapse
|
|
14
|
Patient Preparation and Patient-related Challenges with FDG-PET/CT in Infectious and Inflammatory Disease. PET Clin 2020; 15:125-134. [PMID: 32145883 DOI: 10.1016/j.cpet.2019.11.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Several factors that influence physiologic 18F-fluorodeoxyglucose (FDG) uptake and general FDG distribution may affect PET/CT imaging in infection and inflammation. The general impact of hyperglycemia on the diagnostic performance of FDG-PET/CT is probably less in infection/inflammation than in malignancy. Patient preparation may reduce physiologic FDG uptake, but recommendations are less established than in malignancy. Local implementation of various patient preparatory measures should reflect the specific patient population and indications. This article outlines some of the challenges with physiologic FDG distribution, focusing on infectious and inflammatory diseases, and potential countermeasures and patient preparation to limit physiologic uptake before scan.
Collapse
|
|
15
|
Abstract
International colon cancer guidelines suggest F-FDG PET/CT in a few circumstances: (1) at disease presentation in case of suspected or proven metastatic synchronous adenocarcinoma; (2) in the workup of recurrent colon cancer with metachronous metastases documented by CT, MRI, or biopsy and in case of serial CEA elevation with negative colonoscopy and negative CT; and (3) in case of contraindication to iodine- and gadolinium-based contrast agents. However, review of the literature has shown that PET/CT can also be used in other scenarios with significant levels of diagnostic advantage. This review aims to emphasize differences between guidelines and scientific literature for the use of PET/CT in colon cancer.
Collapse
|
|
16
|
Koepsell H. Glucose transporters in the small intestine in health and disease. Pflugers Arch 2020; 472:1207-1248. [PMID: 32829466 PMCID: PMC7462918 DOI: 10.1007/s00424-020-02439-5] [Citation(s) in RCA: 148] [Impact Index Per Article: 29.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Revised: 07/11/2020] [Accepted: 07/17/2020] [Indexed: 12/23/2022]
Abstract
Absorption of monosaccharides is mainly mediated by Na+-D-glucose cotransporter SGLT1 and the facititative transporters GLUT2 and GLUT5. SGLT1 and GLUT2 are relevant for absorption of D-glucose and D-galactose while GLUT5 is relevant for D-fructose absorption. SGLT1 and GLUT5 are constantly localized in the brush border membrane (BBM) of enterocytes, whereas GLUT2 is localized in the basolateral membrane (BLM) or the BBM plus BLM at low and high luminal D-glucose concentrations, respectively. At high luminal D-glucose, the abundance SGLT1 in the BBM is increased. Hence, D-glucose absorption at low luminal glucose is mediated via SGLT1 in the BBM and GLUT2 in the BLM whereas high-capacity D-glucose absorption at high luminal glucose is mediated by SGLT1 plus GLUT2 in the BBM and GLUT2 in the BLM. The review describes functions and regulations of SGLT1, GLUT2, and GLUT5 in the small intestine including diurnal variations and carbohydrate-dependent regulations. Also, the roles of SGLT1 and GLUT2 for secretion of enterohormones are discussed. Furthermore, diseases are described that are caused by malfunctions of small intestinal monosaccharide transporters, such as glucose-galactose malabsorption, Fanconi syndrome, and fructose intolerance. Moreover, it is reported how diabetes, small intestinal inflammation, parental nutrition, bariatric surgery, and metformin treatment affect expression of monosaccharide transporters in the small intestine. Finally, food components that decrease D-glucose absorption and drugs in development that inhibit or downregulate SGLT1 in the small intestine are compiled. Models for regulations and combined functions of glucose transporters, and for interplay between D-fructose transport and metabolism, are discussed.
Collapse
Affiliation(s)
- Hermann Koepsell
- Institute for Anatomy and Cell Biology, University of Würzburg, Koellikerstr 6, 97070, Würzburg, Germany.
| |
Collapse
|
|
17
|
Schreuder N, Klarenbeek H, Vendel BN, Jager PL, Kosterink JGW, van Puijenbroek EP. Discontinuation of metformin to prevent metformin-induced high colonic FDG uptake: is 48 h sufficient? Ann Nucl Med 2020; 34:833-839. [PMID: 32815120 PMCID: PMC7584522 DOI: 10.1007/s12149-020-01509-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 08/11/2020] [Indexed: 12/14/2022]
Abstract
Objective In this retrospective, single-center observational study, we investigated whether discontinuing metformin for at least 48 h prevents metformin-induced [18F]fluorodeoxyglucose (FDG) uptake in all segments of the colon. Methods Patients with type 2 diabetes who were using metformin before undergoing an FDG PET/CT scan were included. Two groups were created: patients who discontinued metformin for less than 48 h (< 48 h group) and patients who discontinued metformin for between 48 and 72 h (≥ 48 h group). A control group comprised non-diabetic patients who were not using metformin before undergoing an FDG PET/CT. We visually scored the uptake of FDG in four segments of the colon—the ascendens, transversum, descendens, and rectosigmoid—using a four-point scale (1–4) and considered scores of 3 or 4 to be clinically significant. Results Colonic FDG uptake in the ≥ 48 h group (n = 23) was higher than uptake in the control group (n = 96) in the colon descendens [odds ratio (OR) 14.0; 95% confidence interval (CI) 4.8–40.9; p value: 0.001] and rectosigmoid (OR 11.3; 95% CI 4.0–31.9; p value: 0.001), and there was no difference in the colon ascendens and transversum. Colonic FDG uptake in the < 48 h group (n = 25) was higher than uptake in the ≥ 48 h group (n = 23) in the colon transversum (OR 4.8; 95% CI 1.3–18.5; p value: 0.022) and rectosigmoid (p value: 0.023), and there was no difference in the colon ascendens and descendens. Conclusions Discontinuing metformin for 48 h before undergoing an FDG PET/CT still gives a high uptake in the distal parts of the colon when compared with non-diabetic patients who are not using metformin. Discontinuing metformin for 48 h seems to be useful for scanning the more proximal segments of the colon.
Collapse
Affiliation(s)
- Nanno Schreuder
- Groningen Research Institute of Pharmacy, Pharmacotherapy, Epidemiology and Economics, University of Groningen, Antonius Deusinglaan 1, Groningen, The Netherlands.
- GE Healthcare Radiopharmacy Zwolle, Zwolle, The Netherlands.
| | - Hedwig Klarenbeek
- Groningen Research Institute of Pharmacy, Pharmacotherapy, Epidemiology and Economics, University of Groningen, Antonius Deusinglaan 1, Groningen, The Netherlands
| | - Brian N Vendel
- Department of Nuclear Medicine, Isala Hospital, Zwolle, The Netherlands
| | - Pieter L Jager
- Department of Nuclear Medicine, Isala Hospital, Zwolle, The Netherlands
| | - Jos G W Kosterink
- Groningen Research Institute of Pharmacy, Pharmacotherapy, Epidemiology and Economics, University of Groningen, Antonius Deusinglaan 1, Groningen, The Netherlands
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Eugène P van Puijenbroek
- Groningen Research Institute of Pharmacy, Pharmacotherapy, Epidemiology and Economics, University of Groningen, Antonius Deusinglaan 1, Groningen, The Netherlands
- Netherlands Pharmacovigilance Centre Lareb, 's Hertogenbosch, The Netherlands
| |
Collapse
|
|
18
|
Le Fur M, Zhou IY, Catalano O, Caravan P. Toward Molecular Imaging of Intestinal Pathology. Inflamm Bowel Dis 2020; 26:1470-1484. [PMID: 32793946 PMCID: PMC7500524 DOI: 10.1093/ibd/izaa213] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Indexed: 12/13/2022]
Abstract
Inflammatory bowel disease (IBD) is defined by a chronic relapsing and remitting inflammation of the gastrointestinal tract, with intestinal fibrosis being a major complication. The etiology of IBD remains unknown, but it is thought to arise from a dysregulated and excessive immune response to gut luminal microbes triggered by genetic and environmental factors. To date, IBD has no cure, and treatments are currently directed at relieving symptoms and treating inflammation. The current diagnostic of IBD relies on endoscopy, which is invasive and does not provide information on the presence of extraluminal complications and molecular aspect of the disease. Cross-sectional imaging modalities such as computed tomography enterography (CTE), magnetic resonance enterography (MRE), positron emission tomography (PET), single photon emission computed tomography (SPECT), and hybrid modalities have demonstrated high accuracy for the diagnosis of IBD and can provide both functional and morphological information when combined with the use of molecular imaging probes. This review presents the state-of-the-art imaging techniques and molecular imaging approaches in the field of IBD and points out future directions that could help improve our understanding of IBD pathological processes, along with the development of efficient treatments.
Collapse
Affiliation(s)
- Mariane Le Fur
- The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, The Institute for Innovation in Imaging, Massachusetts General Hospital and Harvard Medical School, MA, USA
| | - Iris Y Zhou
- The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, The Institute for Innovation in Imaging, Massachusetts General Hospital and Harvard Medical School, MA, USA
| | - Onofrio Catalano
- The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, The Institute for Innovation in Imaging, Massachusetts General Hospital and Harvard Medical School, MA, USA,The Division of Abdominal Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, MA, USA
| | - Peter Caravan
- The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, The Institute for Innovation in Imaging, Massachusetts General Hospital and Harvard Medical School, MA, USA,Address correspondence to: Peter Caravan, PhD, The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, The Institute for Innovation in Imaging, Massachusetts General Hospital and Harvard Medical School, 149 Thirteenth Street, Charlestown 02129, MA, USA. E-mail:
| |
Collapse
|
|
19
|
Morita Y, Nogami M, Sakaguchi K, Okada Y, Hirota Y, Sugawara K, Tamori Y, Zeng F, Murakami T, Ogawa W. Enhanced Release of Glucose Into the Intraluminal Space of the Intestine Associated With Metformin Treatment as Revealed by [ 18F]Fluorodeoxyglucose PET-MRI. Diabetes Care 2020; 43:1796-1802. [PMID: 32493754 DOI: 10.2337/dc20-0093] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Accepted: 04/06/2020] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Positron emission tomography (PET)-computed tomography has revealed that metformin promotes the intestinal accumulation of [18F]fluorodeoxyglucose (FDG), a nonmetabolizable glucose derivative. It has remained unknown, however, whether this accumulation occurs in the wall or intraluminal space of the intestine. We here addressed this question with the use of [18F]FDG PET-MRI, a recently developed imaging method with increased accuracy of registration and high soft-tissue contrast. RESEARCH DESIGN AND METHODS Among 244 individuals with type 2 diabetes who underwent PET-MRI, we extracted 24 pairs of subjects matched for age, BMI, and HbA1c level who were receiving treatment with metformin (metformin group) or were not (control group). We evaluated accumulation of [18F]FDG in different portions of the intestine with both a visual scale and measurement of maximum standardized uptake value (SUVmax), and such accumulation within the intestinal wall or lumen was discriminated on the basis of SUVmax. RESULTS SUVmax of the jejunum, ileum, and right or left hemicolon was greater in the metformin group than in the control group. [18F]FDG accumulation in the ileum and right or left hemicolon, as assessed with the visual scale, was also greater in the metformin group. SUVmax for the intraluminal space of the ileum and right or left hemicolon, but not that for the intestinal wall, was greater in the metformin group than in the control group. CONCLUSIONS Metformin treatment was associated with increased accumulation of [18F]FDG in the intraluminal space of the intestine, suggesting that this drug promotes the transport of glucose from the circulation into stool.
Collapse
Affiliation(s)
- Yasuko Morita
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Munenobu Nogami
- Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kazuhiko Sakaguchi
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yuko Okada
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yushi Hirota
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kenji Sugawara
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yoshikazu Tamori
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.,Division of Creative Health Promotion, Department of Social/Community Medicine and Health Science, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Feibi Zeng
- Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takamichi Murakami
- Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Wataru Ogawa
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| |
Collapse
|
|
20
|
Chang HS, Kim SJ, Kim YH. Association Between Colonic 18F-FDG Uptake and Glycemic Control in Patients with Diabetes Mellitus. Nucl Med Mol Imaging 2020; 54:168-174. [PMID: 32831962 DOI: 10.1007/s13139-020-00647-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 05/21/2020] [Accepted: 06/11/2020] [Indexed: 12/29/2022] Open
Abstract
Purpose Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (FDG) is a useful imaging modality that visualizes glucose utilization. Diffuse colonic FDG uptake is frequently observed in patients being treated for diabetes mellitus (DM), especially with metformin. The aim of this study was to evaluate whether patients without increased colonic FDG uptake after taking oral hypoglycemic agents (OHA) are associated with insufficient glycemic control. Methods A total of 279 subjects who underwent FDG PET/CT scans for health examinations and had been diagnosed with DM and taken an OHA before the day of the FDG PET/CT were included. Colonic FDG uptake in the study subjects was visually assessed, and the maximal and mean standard uptake value (SUV) was measured. Fasting blood glucose and glycated hemoglobin A1c (HbA1c) levels at both baseline and follow-up visits as well as DM management were compared according to the colonic FDG uptake. Results The mean age of study subjects was 48.8 years old, and 251 of subjects were male. Positive colonic FDG uptake was observed in 200 (71.7%) subjects. Fasting blood glucose and Hb1Ac levels on the day of FDG PET/CT were higher in subjects without positive colonic FDG uptake than those with positive colonic FDG uptake (p ≤ 0.001). But there was no significant difference between the two groups at follow-up visits. Conclusions Patients with DM who did not show increased colonic FDG uptake after taking OHA were associated with higher fasting blood glucose and HbA1c levels on the day of FDG PET/CT.
Collapse
Affiliation(s)
- Hyung Seok Chang
- Department of Nuclear Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29, Saemunan-ro, Jongno-gu, Seoul, 03181 Republic of Korea
| | - Soo Jeong Kim
- Department of Nuclear Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29, Saemunan-ro, Jongno-gu, Seoul, 03181 Republic of Korea
| | - Young Hwan Kim
- Department of Nuclear Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29, Saemunan-ro, Jongno-gu, Seoul, 03181 Republic of Korea
| |
Collapse
|
|
21
|
Edwards KW. Preparation and Logistic Considerations in Performing PET and PET/Computed Tomography in Pediatric Patients. PET Clin 2020; 15:285-292. [PMID: 32498984 DOI: 10.1016/j.cpet.2020.03.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
It is good for the nuclear medicine technologist to be aware of the normal variants and the appearance of a good-quality scan. The primary responsibility as a nuclear medicine technologist is to provide an optimal quality scan that maximizes the reading physician's ability to correctly interpret while using current radiation safety practices as the best possible experience is created for patients and families. Combining the radiation safety aspects (nuclear) with how care is provided (medicine) and the use of the most recent equipment (technology) is what defines a nuclear medicine technologist.
Collapse
|
|
22
|
Beheshti M, Manafi-Farid R, Rezaee A, Langsteger W. PET/CT and PET/MRI, Normal Variations, and Artifacts. Clin Nucl Med 2020. [DOI: 10.1007/978-3-030-39457-8_17] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|
|
23
|
Sheikh A, Anolik J, Maurer AH. Update on Serum Glucose and Metabolic Management of Clinical Nuclear Medicine Studies: Current Status and Proposed Future Directions. Semin Nucl Med 2019; 49:411-421. [PMID: 31470934 DOI: 10.1053/j.semnuclmed.2019.06.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Management of a patient's blood glucose or metabolism in nuclear medicine studies has become an integral aspect of daily work primarily due to the increasing use of F-18 flurodeoxyglucose (FDG) positron emission tomography (PET). Newer tracers such as F-18 Fluciclovine and C-11 Choline, are in theory subject to metabolic shifts and changes based on patients' insulin levels, and also require attention to achieving optimum patient preparation. Metabolic derangements can also affect other studies, such as gastric emptying (GE), the results of which are dependent upon the patient's blood glucose level during the time of imaging. The growing variety of diabetic medications has increased the complexity of the instructions which need to be given to patients. Current guidelines for patient preparation were developed in the past and have only slowly evolved with the introduction of newer oral medications. In addition to older insulin formulations newer formulations with different profiles of onset, duration, and consistency of action are being used. The wide spectrum of newer drugs now in use for treating diabetes has not been accompanied by any updated consensus on how to manage these drugs for imaging studies which require blood glucose level management. In this article we review these newer diabetes medications primarily to raise awareness of the changing landscape. Our focus will be on suggestions to optimize patient preparation and management for these studies. For each scenario, our suggestions will be given as summary proposals for best patient management. Our hope is that this discussion will stimulate multicenter studies to provide data to support new practice guidelines for metabolically dependent nuclear medicine procedures.
Collapse
Affiliation(s)
- Arif Sheikh
- Division of Nuclear Medicine; Department of Diagnostic, Molecular and Interventional Radiology, Mount Sinai Hospital, Icahn School of Medicine, New York, NY.
| | - Jonathan Anolik
- Section of Endocrinology, Department of Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, PA
| | - Alan H Maurer
- Section of Nuclear Medicine, Department of Radiology, Temple University Lewis Katz School of Medicine, Philadelphia, PA
| |
Collapse
|
|
24
|
Metformin acutely lowers blood glucose levels by inhibition of intestinal glucose transport. Sci Rep 2019; 9:6156. [PMID: 30992489 PMCID: PMC6468119 DOI: 10.1038/s41598-019-42531-0] [Citation(s) in RCA: 77] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 04/02/2019] [Indexed: 12/22/2022] Open
Abstract
Metformin is currently the most prescribed drug for treatment of type 2 diabetes mellitus in humans. It has been well established that long-term treatment with metformin improves glucose tolerance in mice by inhibiting hepatic gluconeogenesis. Interestingly, a single dose of orally administered metformin acutely lowers blood glucose levels, however, little is known about the mechanism involved in this effect. Glucose tolerance, as assessed by the glucose tolerance test, was improved in response to prior oral metformin administration when compared to vehicle-treated mice, irrespective of whether the animals were fed either the standard or high-fat diet. Blood glucose-lowering effects of acutely administered metformin were also observed in mice lacking functional AMP-activated protein kinase, and were independent of glucagon-like-peptide-1 or N-methyl-D-aspartate receptors signaling. [18F]-FDG/PET revealed a slower intestinal transit of labeled glucose after metformin as compared to vehicle administration. Finally, metformin in a dose-dependent but indirect manner decreased glucose transport from the intestinal lumen into the blood, which was observed ex vivo as well as in vivo. Our results support the view that the inhibition of transepithelial glucose transport in the intestine is responsible for lowering blood glucose levels during an early response to oral administration of metformin.
Collapse
|
|
25
|
Steenkamp DW, McDonnell ME, Meibom S. Metformin may be associated with false-negative cancer detection in the gastrointestinal tract on PET/CT. Endocr Pract 2019; 20:1079-83. [PMID: 25100379 DOI: 10.4158/ep14127.ra] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
OBJECTIVE Concurrent therapy with the antihyperglycemic drug metformin can hinder the detection of malignancy in the abdominal and pelvic portions of 18F-fluordeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging performed for the diagnosis or staging of malignancy, as well as for treatment response and radiation therapy planning. This is due to the metformin-induced increase in intestinal FDG radiotracer uptake. We aim to bring this potentially important interaction to the attention of clinicians who care for cancer patients with diabetes. METHODS We searched MEDLINE (from 1970 to January 2014) and Google Scholar for relevant English-language articles using the following search terms: "metformin and FDG/PET, metformin and bowel uptake, metformin, and cancer, metformin and the intestine, metformin pharmacokinetics, hyperglycemia and FDG/PET." We reviewed the reference lists of pertinent articles with respect to metformin gut physiology, impact on FDG uptake and the effect on diagnostic accuracy of abdominalpelvic PET/CT scans with concurrent metformin therapy. RESULTS We reviewed the action of metformin in the intestine, with particular emphasis on the role of metformin in PET/CT imaging and include a discussion of clinical studies on the topic to help refine knowledge and inform practice. Finally, we discuss aspects pertinent to the management of type 2 diabetes (T2D) patients on metformin undergoing PET/CT. CONCLUSIONS Metformin leads to intense, diffusely increased FDG uptake in the colon, and to a lesser degree, the small intestine, which limits the diagnostic capabilities of FDG PET/CT scanning and may mask gastrointestinal malignancies. We suggest that metformin be discontinued 48 hours before FDG PET/CT scanning is performed in oncology patients. More rigorous data are needed to support the widespread generalizability of this recommendation.
Collapse
Affiliation(s)
- Devin W Steenkamp
- Section of Endocrinology, Diabetes and Nutrition, Boston Medical Center, Boston University School of Medicine
| | - Marie E McDonnell
- Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School
| | - Sara Meibom
- Section of Nuclear Medicine, Department of Radiology, Boston Medical Center/Boston University School of Medicine, Boston, Massachusetts
| |
Collapse
|
|
26
|
Diffuse Intense Intestinal FDG Activity in a Patient With Familial Adenomatous Polyposis. Clin Nucl Med 2019; 44:262-264. [PMID: 30589675 DOI: 10.1097/rlu.0000000000002438] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Familial adenomatous polyposis is a rare autosomal dominant intestinal syndrome with a high rate of malignant transformation. Here, we report a 20-year-old woman with a diagnosis of familial adenomatous polyposis by pathologic examination after colonoscopy biopsy, who underwent an F-FDG PET/CT to assess the extent of this disease. The images showed diffuse elevated FDG uptake along the entire colorectum. Additionally, focal enlarged lymph nodes with increased FDG uptake were noted. These findings promoted proctocolectomy and lymphadenectomy.
Collapse
|
|
27
|
Franquet E, Watts G, Kolodny GM, Goldfine AB, Patti ME. PET-CT reveals increased intestinal glucose uptake after gastric surgery. Surg Obes Relat Dis 2019; 15:643-649. [PMID: 30773442 DOI: 10.1016/j.soard.2019.01.018] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Revised: 01/16/2019] [Accepted: 01/18/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND Mechanisms of metabolic improvement after bariatric surgery remain incompletely understood. Intestinal glucose uptake is increased after gastric bypass in rodents, potentially contributing to reduced blood glucose and type 2 diabetes remission. OBJECTIVE We assessed whether intestinal glucose uptake is increased in humans after gastric surgery. SETTING University Hospital, United States. METHODS In a retrospective, case-control cohort study, positron emission tomography-computerized tomography scans performed for clinical indications were analyzed to quantify intestinal glucose uptake in patients with or without history of gastric surgery. We identified 19 cases, defined as patients over age 18 with prior gastric surgery (Roux-en-Y gastric bypass [n = 10], sleeve gastrectomy [n = 1], or Billroth I [n = 2] or II gastrectomy [n = 6]), and 43 controls without gastric surgery, matched for age, sex, and indication for positron emission tomography-computerized tomography. Individuals with gastrointestinal malignancy or metformin treatment were excluded. Images were obtained 60 minutes after 18F-fluorodeoxyglucose injection (4.2 MBq/kg), and corrected by attenuation; noncontrast low-dose computerized tomography was obtained in parallel. Fused and nonfused images were analyzed; standardized uptake values were calculated for each region by volumes of interest at the region of highest activity. RESULTS Both standardized uptake values maximum and mean were significantly increased by 41% to 98% in jejunum, ascending, and transverse colon in patients with prior gastric surgery (P < .05 versus controls). CONCLUSION Intestinal glucose uptake is increased in patients with prior gastric surgery. Prospective studies are important to dissect the contributions of weight loss, dietary factors, and systemic metabolism, and to determine the relationship with increased insulin-independent glucose uptake and reductions in glycemia.
Collapse
Affiliation(s)
- Elisa Franquet
- Division of Nuclear Medicine, Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts
| | - George Watts
- Division of Nuclear Medicine, Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts
| | - Gerald M Kolodny
- Division of Nuclear Medicine, Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts
| | - Allison B Goldfine
- Research Division, Joslin Diabetes Center, and Harvard Medical School, Boston, Massachusetts
| | - Mary-Elizabeth Patti
- Research Division, Joslin Diabetes Center, and Harvard Medical School, Boston, Massachusetts.
| |
Collapse
|
|
28
|
Kaiser A, Davenport MS, Frey KA, Greenspan B, Brown RKJ. Management of Diabetes Mellitus Before 18F-Fluorodeoxyglucose PET/CT: A Nationwide Patient-Centered Assessment of Approaches to Examination Preparation. J Am Coll Radiol 2018; 16:804-809. [PMID: 30348616 DOI: 10.1016/j.jacr.2018.09.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Accepted: 09/06/2018] [Indexed: 01/17/2023]
Abstract
PURPOSE The aim of this study was to perform, from the patient's point of view, a nationwide assessment of nuclear medicine practices regarding diabetic management before 18F-fluorodeoxyglucose (FDG) PET/CT for oncologic indications. METHODS This prospective observational study was exempt from institutional review board oversight. Sixty-five nuclear medicine scheduling lines (33 academic, 32 private practice, 12-17 in each of the five US regions) were called using a prewritten script under the guise of a nonexpert patient's family member about scheduling a patient with diabetes with "cancer" for FDG PET/CT. Each center was called three times on three different days. The following data were collected: (1) blood glucose threshold for rescheduling an examination, (2) when or if to stop various medications, (3) fasting requirements, and (4) time-of-day scheduling preferences. Withheld information was not specifically requested. Descriptive statistics were calculated. RESULTS There were 195 phone calls (mean duration, 2.9 min; range, 2-6 min). Relevant information was often withheld; withholding rates were as follows: blood glucose threshold, 71% (138 of 195); short-acting insulin instructions, 30% (59 of 195); long-acting insulin instructions, 99% (193 of 195); metformin instructions, 88% (179 of 195); fasting duration, 37% (72 of 195); and time-of-day scheduling preference, 91% (177 of 195). Mean provided data were as follows: blood glucose threshold, 195 mg/dL (range, 150-210 mg/dL); short-acting insulin withholding, 4.9 hours (range, 4-8 hours); long-acting insulin withholding, 12 hours (range, 12-24 hours); fasting duration, 5 hours (range, 4-8 hours); and preferred examination time, 91% (177 of 195). When specified (n = 18), morning scheduling was preferred (8% [15 of 195] versus 2% [3 of 195]). CONCLUSIONS Diabetes-specific information is commonly withheld by nuclear medicine call centers throughout the United States when discussing oncologic FDG PET/CT despite local and national policies indicating its importance.
Collapse
Affiliation(s)
- Andrew Kaiser
- Department of Radiology, University of Michigan, Ann Arbor, Michigan.
| | | | - Kirk A Frey
- Department of Radiology, University of Michigan, Ann Arbor, Michigan
| | - Bennett Greenspan
- Department of Radiology, Medical College of Georgia, Augusta, Georgia
| | - Richard K J Brown
- Department of Radiology, University of Michigan, Ann Arbor, Michigan
| |
Collapse
|
|
29
|
Enhanced intestinal 2-deoxy-2-[18F]fluoro-D-glucose uptake under metformin is not fully suppressed by loperamide. Endocr Regul 2018; 52:185-191. [PMID: 31517614 DOI: 10.2478/enr-2018-0023] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
OBJECTIVE This study investigated whether the metformin (Met)-induced enhanced intestinal uptake of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) is reduced by loperamide, a long-acting anti-diarrheal agent. METHODS Mean 18F-FDG uptake in the mouse small intestine and colon with Met exposure was compared with that in control mice. In the Met group, high-dose (1.0 mg/kg body weight) and low-dose (0.1 mg/kg body weight) loperamide were introduced, and 18F-FDG uptake in the small intestine and colon was compared with that of control mice administered high-dose loperamide. The percent injected dose of 18F-FDG per gram of tissue (%ID/g) in the extracted tissues was then determined. RESULTS 18F-FDG uptake increased significantly in the small intestine (0.64±0.06 vs. 1.01±0.15, p=0.040) and, especially, the colon (0.46±0.13 vs. 2.16±0.51, p<0.001) after Met exposure. Neither high-dose nor low-dose loperamide significantly reduced 18F-FDG uptake in the small intestine (0.82±0.31 vs. 0.84±0.22, p=0.93 and 0.78±0.25 vs. 0.70±0.15, p=0.13, respectively) or colon (2.13±0.41 vs. 1.67±0.55, p=0.063 and 1.77±0.39 vs. 1.80±0.25, p=0.56, respectively). The colonic %ID/g was significantly higher in Met groups irrespective of loperamide introduction than in control group, whereas the significant difference in the small intestine was observed only between Met and control groups. CONCLUSION Metformin increased 18F-FDG uptake in intestines especially in colon. Loperamide administration partially, but not sufficiently, suppresses the Met-induced increased colonic uptake of 18F-FDG.
Collapse
|
|
30
|
Catalano O, Kilcoyne A, Signore A, Mahmood U, Rosen B. Lower Gastrointestinal Tract Applications of PET/Computed Tomography and PET/MR Imaging. Radiol Clin North Am 2018; 56:821-834. [PMID: 30119776 DOI: 10.1016/j.rcl.2018.05.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This article discusses the role of PET/CT and PET/MR imaging in the evaluation of inflammatory and malignant disorders of the lower gastrointestinal tract. This includes a review of the current literature and a discussion of new and emerging research.
Collapse
|
|
31
|
Affiliation(s)
- Steve Y Cho
- From the Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, University of Wisconsin School of Medicine and Public Health, University of Wisconsin Carbone Cancer Center, 1111 Highland Ave, WIMR1, Room 7139, Madison, WI 53705
| |
Collapse
|
|
32
|
Hamidizadeh R, Eftekhari A, Wiley EA, Wilson D, Alden T, Bénard F. Metformin Discontinuation prior to FDG PET/CT: A Randomized Controlled Study to Compare 24- and 48-hour Bowel Activity. Radiology 2018; 289:418-425. [PMID: 30106348 DOI: 10.1148/radiol.2018180078] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Purpose To investigate the relationship of 24- and 48-hour metformin discontinuation to bowel uptake of fluorine 18 fluorodeoxyglucose (FDG) on PET/CT scans. Materials and Methods Patients with diabetes who were treated with metformin and referred for FDG PET/CT were randomized to three equal groups based on duration of metformin discontinuation: 24 hours, 48 hours, and no discontinuation (control group). Two interpreters blinded to the study groups assessed FDG uptake in multiple segments of small and large bowel qualitatively and semiquantitatively by using maximum standardized uptake values (SUVsmax). Differences in age, sex, weight, dose of metformin, duration of metformin treatment, blood glucose levels, and FDG dose injected were assessed. Data were analyzed with analysis of variance when passing normality, and by nonparametric testing when not. Results Ninety study participants (62 male, 28 female; median age, 70 years) were enrolled from July 2010 through March 2012. There were no differences between study groups in weight, blood glucose levels 3 days prior to scanning, or normal organ uptake. Large bowel SUVmax was lower after 24 hours (4.10 ± 2.00 vs 5.42 ± 2.36; P = .020) and 48 hours (2.63 ± 0.88 vs 5.42 ± 2.36; P ˂ .001) of metformin discontinuation than for no discontinuation (control), and for 48 hours versus 24 hours of discontinuation (P = .0015). Small bowel SUVmax was lower after 24 hours (2.86 ± 0.67 vs 3.73 ± 1.08 [control]; P ˂ .001) and 48 hours (2.78 ± 0.73 vs 3.73 ± 1.08 [control]; P ˂ .001) of metformin discontinuation versus no metformin discontinuation, but not for 48 hours versus 24 hours of discontinuation (P = .57). Examination-day blood glucose levels increased after 48-hour withdrawal of metformin (8.41 mmol/L ± 2.86 vs 6.83 mmol/L ± 2.13 [control]; P = .002). Conclusion Metformin discontinuation for 48 hours prior to PET/CT was associated with lower accumulation of fluorodeoxyglucose in the bowel, compared to when there was no discontinuation (control group) or 24-hour discontinuation of metformin. © RSNA, 2018.
Collapse
Affiliation(s)
- Ramin Hamidizadeh
- From the Faculty of Medicine (R.H.) and Department of Radiology (D.W., F.B.), University of British Columbia, Vancouver, BC, Canada; BC Cancer, BC Cancer Research Centre, 675 W 10th Ave, Vancouver, BC, Canada V5Z 1L3 (A.E., D.W., T.A., F.B.); Department of Diagnostic Radiology, Surrey Memorial Hospital, Surrey, BC, Canada (A.E.); and Department of Nuclear Medicine, QEII Health Sciences Centre, Halifax, NS, Canada (A.W.)
| | - Arash Eftekhari
- From the Faculty of Medicine (R.H.) and Department of Radiology (D.W., F.B.), University of British Columbia, Vancouver, BC, Canada; BC Cancer, BC Cancer Research Centre, 675 W 10th Ave, Vancouver, BC, Canada V5Z 1L3 (A.E., D.W., T.A., F.B.); Department of Diagnostic Radiology, Surrey Memorial Hospital, Surrey, BC, Canada (A.E.); and Department of Nuclear Medicine, QEII Health Sciences Centre, Halifax, NS, Canada (A.W.)
| | - E Ashley Wiley
- From the Faculty of Medicine (R.H.) and Department of Radiology (D.W., F.B.), University of British Columbia, Vancouver, BC, Canada; BC Cancer, BC Cancer Research Centre, 675 W 10th Ave, Vancouver, BC, Canada V5Z 1L3 (A.E., D.W., T.A., F.B.); Department of Diagnostic Radiology, Surrey Memorial Hospital, Surrey, BC, Canada (A.E.); and Department of Nuclear Medicine, QEII Health Sciences Centre, Halifax, NS, Canada (A.W.)
| | - Don Wilson
- From the Faculty of Medicine (R.H.) and Department of Radiology (D.W., F.B.), University of British Columbia, Vancouver, BC, Canada; BC Cancer, BC Cancer Research Centre, 675 W 10th Ave, Vancouver, BC, Canada V5Z 1L3 (A.E., D.W., T.A., F.B.); Department of Diagnostic Radiology, Surrey Memorial Hospital, Surrey, BC, Canada (A.E.); and Department of Nuclear Medicine, QEII Health Sciences Centre, Halifax, NS, Canada (A.W.)
| | - Tina Alden
- From the Faculty of Medicine (R.H.) and Department of Radiology (D.W., F.B.), University of British Columbia, Vancouver, BC, Canada; BC Cancer, BC Cancer Research Centre, 675 W 10th Ave, Vancouver, BC, Canada V5Z 1L3 (A.E., D.W., T.A., F.B.); Department of Diagnostic Radiology, Surrey Memorial Hospital, Surrey, BC, Canada (A.E.); and Department of Nuclear Medicine, QEII Health Sciences Centre, Halifax, NS, Canada (A.W.)
| | - François Bénard
- From the Faculty of Medicine (R.H.) and Department of Radiology (D.W., F.B.), University of British Columbia, Vancouver, BC, Canada; BC Cancer, BC Cancer Research Centre, 675 W 10th Ave, Vancouver, BC, Canada V5Z 1L3 (A.E., D.W., T.A., F.B.); Department of Diagnostic Radiology, Surrey Memorial Hospital, Surrey, BC, Canada (A.E.); and Department of Nuclear Medicine, QEII Health Sciences Centre, Halifax, NS, Canada (A.W.)
| |
Collapse
|
|
33
|
Boursi B, Werner TJ, Gholami S, Houshmand S, Mamtani R, Lewis JD, Wu GD, Alavi A, Yang YX. Functional imaging of the interaction between gut microbiota and the human host: A proof-of-concept clinical study evaluating novel use for 18F-FDG PET-CT. PLoS One 2018; 13:e0192747. [PMID: 29447210 PMCID: PMC5813966 DOI: 10.1371/journal.pone.0192747] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Accepted: 01/30/2018] [Indexed: 12/19/2022] Open
Abstract
Recent data comparing germ-free to conventionally-raised mice demonstrated that energy homeostasis of colonocytes is dependent on gut microbiota through regulation of short chain fatty acids (SCFA) production and glucose utilization. We sought to evaluate 18F-FDG PET-CT as a novel technique for functional imaging of alterations in glucose metabolism as a result of the interaction between the gut microbiota and the human host. We conducted a prospective study in healthy humans that underwent 18F-FDG PET-CT and sampling of the gut microbiota before and after orally administered broad-spectrum antibiotics. The primary outcomes were total and regional physiologic colonic 18F-FDG uptake (measured as the mean and max standardized uptake values [SUVmean and SUVmax]). The study demonstrated significant increases in physiologic colonic 18F-FDG uptake in all study participants following antibiotic treatment and a 4-5log reduction of gut bacterial load. The mean increase in SUVmax was 0.63±0.37 SD (p = 0.004) and the median increase was 0.42 with an IQR of 0.40–0.81. The mean increase in SUVmean was 0.31±0.24 SD (p = 0.01) and the median increase was 0.41 with an IQR of 0.06–0.55. A likely explanation for this phenomenon is a shift in colonocyte metabolism to glycolysis due to a shortage of SCFA.
Collapse
Affiliation(s)
- Ben Boursi
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
- Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
- Tel-Aviv University, Tel-Aviv, Israel
- Department of Oncology, Sheba Medical Center, Tel Hashomer, Ramat-Gan, Israel
- * E-mail:
| | - Thomas J. Werner
- Department of Nuclear Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Saeid Gholami
- Department of Nuclear Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Sina Houshmand
- Department of Nuclear Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Ronac Mamtani
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
- Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - James D. Lewis
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Gary D. Wu
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Abass Alavi
- Department of Nuclear Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Yu-Xiao Yang
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| |
Collapse
|
|
34
|
|
|
35
|
Bahler L, Holleman F, Chan MW, Booij J, Hoekstra JB, Verberne HJ. 18F-FDG uptake in the colon is modulated by metformin but not associated with core body temperature and energy expenditure. PLoS One 2017; 12:e0176242. [PMID: 28464031 PMCID: PMC5413044 DOI: 10.1371/journal.pone.0176242] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Accepted: 04/06/2017] [Indexed: 12/30/2022] Open
Abstract
Purpose Physiological colonic 18F-fluorodeoxyglucose (18F-FDG) uptake is a frequent finding on 18F-FDG positron emission tomography computed tomography (PET-CT). Interestingly, metformin, a glucose lowering drug associated with moderate weight loss, is also associated with an increased colonic 18F-FDG uptake. Consequently, increased colonic glucose use might partly explain the weight losing effect of metformin when this results in an increased energy expenditure and/or core body temperature. Therefore, we aimed to determine whether metformin modifies the metabolic activity of the colon by increasing glucose uptake. Methods In this open label, non-randomized, prospective mechanistic study, we included eight lean and eight overweight males. We measured colonic 18F-FDG uptake on PET-CT, energy expenditure and core body temperature before and after the use of metformin. The maximal colonic 18F-FDG uptake was measured in 5 separate segments (caecum, colon ascendens,—transversum,—descendens and sigmoid). Results The maximal colonic 18F-FDG uptake increased significantly in all separate segments after the use of metformin. There was no significant difference in energy expenditure or core body temperature after the use of metformin. There was no correlation between maximal colonic 18F-FDG uptake and energy expenditure or core body temperature. Conclusion Metformin significantly increases colonic 18F-FDG uptake, but this increased uptake is not associated with an increase in energy expenditure or core body temperature. Although the colon might be an important site of the glucose plasma lowering actions of metformin, this mechanism of action does not explain directly any associated weight loss.
Collapse
Affiliation(s)
- Lonneke Bahler
- Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands
- * E-mail:
| | - Frits Holleman
- Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands
| | - Man-Wai Chan
- Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands
| | - Jan Booij
- Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands
| | - Joost B. Hoekstra
- Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands
| | - Hein J. Verberne
- Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands
| |
Collapse
|
|
36
|
Khalil MM. Basics and Advances of Quantitative PET Imaging. BASIC SCIENCE OF PET IMAGING 2017:303-322. [DOI: 10.1007/978-3-319-40070-9_13] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
37
|
Metformin discontinuation less than 72 h is suboptimal for F-18 FDG PET/CT interpretation of the bowel. Ann Nucl Med 2016; 30:629-636. [PMID: 27392947 DOI: 10.1007/s12149-016-1106-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2016] [Accepted: 07/03/2016] [Indexed: 12/15/2022]
Abstract
OBJECTIVE Metformin-induced [F-18] fluorodeoxyglucose (FDG) bowel uptake can hinder positron emission tomography/computed tomography (PET/CT) evaluation of the bowel. This study aimed to investigate the segmental bowel uptake of FDG according to metformin discontinuation times up to 72 h. METHODS We retrospectively divided 240 diabetic patients into four groups: metformin discontinuation <24 h (group A; n = 86), 24-48 h (group B; n = 40), 48-72 h (group C; n = 12), and no metformin (control group; n = 102). Segmental FDG bowel uptakes were measured visually (four-point scale) and semi-quantitatively (maximum standardized uptake value). RESULTS Compared with the control group, FDG uptake increased significantly from the ileum to the rectosigmoid colon in group A, from the transverse to the rectosigmoid colon in group B, and from the descending colon to the rectosigmoid colon in group C in both visual and semi-quantitative analyses. CONCLUSIONS Metformin discontinuation for <72 h is likely suboptimal for PET/CT image interpretation, especially with respect to the distal segments of the colon.
Collapse
|
|
38
|
Bahler L, Stroek K, Hoekstra JB, Verberne HJ, Holleman F. Metformin-related colonic glucose uptake; potential role for increasing glucose disposal?--A retrospective analysis of (18)F-FDG uptake in the colon on PET-CT. Diabetes Res Clin Pract 2016; 114:55-63. [PMID: 27103370 DOI: 10.1016/j.diabres.2016.02.009] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2015] [Revised: 02/11/2016] [Accepted: 02/18/2016] [Indexed: 12/13/2022]
Abstract
AIM The use of metformin has been associated with diffusely increased colonic (18)F-fluorodeoxyglucose ((18)F-FDG) uptake. Interestingly, metformin use is associated with moderate weight loss. It could be hypothesized that increased colonic glucose disposal is related to this weight loss. It is unknown whether other factors influence (18)F-FDG uptake in the colon. The aim of this study was to retrospectively assess independent determinants of colonic (18)F-FDG uptake. METHODS We retrospectively analysed 270 (18)F-FDG PET-CTs which were made for diagnostic purposes. Colonic (18)F-FDG uptake was assessed using a 4-point scale using the liver as a reference (1; lower, 2; similar, 3; moderately higher than hepatic activity, 4; intense diffuse increased uptake). Determinants of (18)F-FDG uptake in the colon were assessed using forward logistic regression (i.e., grade 1&2 vs 3&4). RESULTS The patients had a mean age of 60.2±14.8 years, a BMI of 25.8±5.2kg/m(2) and 52% were female. Most patients had a grade 2 (44%) or grade 3 (39%) (18)F-FDG uptake in the colon. Diabetes mellitus type 2 was observed in 14% of the patients. In total, 5% of the patients used insulin, 12% used metformin and 5% used sulfonylurea derivatives (SU). While there seemed to be an effect of SU on (18)F-FDG uptake in the ileum [OR 3.6 (95% CI: 1.3-33.1), p=0.03], metformin was the only drug associated with (18)F-FDG uptake for both the whole colon [OR 10.0 (95% CI: 2.9-34.7), p<0.001] and all individual segments. CONCLUSION Metformin use is an independent determinant of increased colonic (18)F-FDG uptake, suggesting a potential role for increasing colonic glucose disposal.
Collapse
Affiliation(s)
- Lonneke Bahler
- Internal Medicine, Academic Medical Center, F4-257, P.O. Box 22660, Amsterdam 1100DD, The Netherlands.
| | - Kevin Stroek
- Internal Medicine, Academic Medical Center, F4-257, P.O. Box 22660, Amsterdam 1100DD, The Netherlands
| | - Joost B Hoekstra
- Internal Medicine, Academic Medical Center, F4-257, P.O. Box 22660, Amsterdam 1100DD, The Netherlands
| | - Hein J Verberne
- Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands
| | - Frits Holleman
- Internal Medicine, Academic Medical Center, F4-257, P.O. Box 22660, Amsterdam 1100DD, The Netherlands
| |
Collapse
|
|
39
|
Lee LK, Kilcoyne A, Goldberg-Stein S, Chow DZ, Lee SI. FDG PET-CT of Genitourinary and Gynecologic Tumors: Overcoming the Challenges of Evaluating the Abdomen and Pelvis. Semin Roentgenol 2015; 51:2-11. [PMID: 27020231 DOI: 10.1053/j.ro.2015.12.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Leslie K Lee
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
| | - Aoife Kilcoyne
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Shlomit Goldberg-Stein
- Department of Radiology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY
| | - David Z Chow
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Susanna I Lee
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| |
Collapse
|
|
40
|
Capitanio S, Marini C, Sambuceti G, Morbelli S. Metformin and cancer: Technical and clinical implications for FDG-PET imaging. World J Radiol 2015; 7:57-60. [PMID: 25825634 PMCID: PMC4374089 DOI: 10.4329/wjr.v7.i3.57] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2014] [Revised: 01/15/2015] [Accepted: 02/09/2015] [Indexed: 02/06/2023] Open
Abstract
Metformin is the most widely used hypoglycemic agent. Besides its conventional indications, increasing evidence demonstrate a potential efficacy of this biguanide as an anticancer drug. Possible mechanisms of actions seem to be independent from its hypoglycemic effect and seem to involve the interference with key pathways in cellular proliferation and glycolysis. To date, many clinical trials implying the use of metformin in cancer treatment are on-going. The increasing use of 18F-2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in cancer evaluation raises a number of questions about the possible interference of the biguanide on FDG distribution. In particular, the interferences exerted by metformin on AMP-activated protein kinase pathway (the cellular energy sensor), on insulin levels and on Hexokinase could potentially have repercussion on glucose handling and thus on FDG distribution. A better comprehension of the impact of metformin on FDG uptake is needed in order to optimize the use of PET in this setting. This evaluation would be useful to ameliorate scans interpretation in diabetic patients under chronic metformin treatment and to critically interpret images in the context of clinical trials. Furthermore, collecting prospective data in this setting would help to verify whether FDG-PET could be a valid tool to appreciate the anticancer effect of this new therapeutic approach.
Collapse
|
|
41
|
Abstract
PET/CT imaging has become an important part of the evaluation of patients with many types of cancer. This imaging modality can also be used to image areas of active inflammation, such as those occurring in patients with active inflammatory bowel disease (IBD) (Crohn's disease and ulcerative colitis). The standard methods of determining a patient's disease activity are either indirect, such as blood and stool tests, or invasive, such as colonoscopy. FDG-PET imaging is a noninvasive, direct method of evaluating bowel inflammation and represents a significant advancement in the care of these patients. The PET/CT technique is very similar to that used for oncology imaging. Minor changes can be instituted to improve the accuracy, as well as to reduce the radiation exposure to the patient. This paper reviews the literature on the use of FDG-PET imaging in IBD in both the adult and pediatric populations. Future improvements in the technique should focus on decreasing the radiation dose to the patient and on decreasing the cost of the examination. The FDG-PET/CT technique is an excellent method for the noninvasive quantification of bowel inflammation in patients with IBD.
Collapse
Affiliation(s)
- Scott B Perlman
- The University of Wisconsin School of Medicine and Public Health, Madison, WI.
| | | | | |
Collapse
|
|
42
|
Bevilacqua T, Greene GS. Diffuse bowel uptake of 18F-FDG on PET/CT examination of a patient with diabetes treated with metformin. BMJ Case Rep 2014; 2014:bcr-2013-202058. [PMID: 24700035 DOI: 10.1136/bcr-2013-202058] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Affiliation(s)
- Thomas Bevilacqua
- Department of Radiology, Pennsylvania Hospital, Philadelphia, Pennsylvania, USA
| | | |
Collapse
|
|
43
|
|
|
44
|
|
|
45
|
Ozguven MA, Karacalioglu AO, Ince S, Emer MO. Altered biodistribution of FDG in patients with type-2 diabetes mellitus. Ann Nucl Med 2014; 28:505-11. [DOI: 10.1007/s12149-014-0840-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2013] [Accepted: 03/10/2014] [Indexed: 12/12/2022]
|
|
46
|
18F-FDG PET/CT for the assessment of gastrointestinal GVHD: results of a pilot study. Bone Marrow Transplant 2013; 49:131-7. [PMID: 24076550 DOI: 10.1038/bmt.2013.144] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2013] [Revised: 07/31/2013] [Accepted: 08/07/2013] [Indexed: 01/25/2023]
Abstract
This prospective pilot study aimed to evaluate the predictive value of (18)F-FDG PET/CT for early diagnosis of acute gastrointestinal GVHD (GI-GVHD). In all, 42 consecutive patients who received allo-SCT were included. (18)F-FDG PET/CT was systematically performed at a median of 28 (range, 24-38) days after allo-SCT. (18)F-FDG PET/CT data review was positive in 15 cases (36%) (9 true positive (TP) cases and 6 false positive (FP) cases) and negative in 27 cases (64%; 26 true negative (TN) cases and 1 false negative (FN) case) at visual analysis. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of (18)F-FDG PET/CT for the diagnosis of acute GI-GVHD were, respectively, 81%, 90%, 60%, 96% and 83%. There were no significant differences of SUVmax values between grade 1-2 GI-GVHD and severe grade 3-4 GI-GVHD. Overall, these preliminary findings suggested that the inflammatory activity of the gastrointestinal tract associated with acute GI-GVHD could be assessed by (18)F-FDG PET/CT suggesting that noninvasive (18)F-FDG PET/CT could become a valuable examination to be performed shortly before endoscopy to map acute GI-GVHD lesions, guide the biopsy sites and choose the appropriate endoscopic procedure, especially in those asymptomatic patients with a positive (18)F-FDG PET/CT.
Collapse
|
|
47
|
Skinner HD, McCurdy MR, Echeverria AE, Lin SH, Welsh JW, O'Reilly MS, Hofstetter WL, Ajani JA, Komaki R, Cox JD, Sandulache VC, Myers JN, Guerrero TM. Metformin use and improved response to therapy in esophageal adenocarcinoma. Acta Oncol 2013; 52:1002-9. [PMID: 22950385 DOI: 10.3109/0284186x.2012.718096] [Citation(s) in RCA: 85] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
BACKGROUND We investigated the radiographic and pathologic response rate of esophageal adenocarcinoma treated with neoadjuvant chemoradiation in patients taking metformin. MATERIAL AND METHODS Two hundred eighty-five patients with esophageal adenocarcinoma treated with concurrent chemoradiation (CRT) followed by esophagectomy from 1997 to 2012 were included in the study, including 29 diabetics taking metformin, 21 diabetics not taking metformin and 235 non-diabetics. Pre- and post-treatment positron emission tomography (PET) scans were available for 204 patients. Pathologic response was graded at the time of surgery. Response rates were compared using both the χ(2) statistic as well as ANOVA with post-hoc LSD analysis. Multivariate logistic regression analysis was performed to control for predictors of pathologic complete response (CR) after CRT. RESULTS The overall rate of pathologic CR for the study population was 20%. The pathologic CR rate was higher in patients taking metformin (34.5%), compared to diabetic patients not taking metformin (4.8%, p = 0.01) and non-diabetic patients (19.6%, p = 0.05). Pathologic CR was related to metformin dose, with ≥ 1500 mg/d associated with a higher CR rate. No significant difference seen in pre-CRT maximum tumor SUV (p = 0.93), however post-CRT maximum SUV was significantly decreased in patients taking metformin (p = 0.05). On multivariate logistic regression, metformin use was independently associated with pathologic CR (p = 0.04). Metformin use was also associated with decreased in field loco-regional failure following radiation (p = 0.05). CONCLUSION Metformin use is associated with a dose-dependent increased response to CRT in esophageal cancer and may be a sensitizer to this therapy.
Collapse
Affiliation(s)
- Heath D Skinner
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
48
|
Habibollahi P, van den Berg NS, Kuruppu D, Loda M, Mahmood U. Metformin--an adjunct antineoplastic therapy--divergently modulates tumor metabolism and proliferation, interfering with early response prediction by 18F-FDG PET imaging. J Nucl Med 2013; 54:252-8. [PMID: 23376854 DOI: 10.2967/jnumed.112.107011] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
UNLABELLED Over the last several years, epidemiologic data have suggested that the antidiabetes drug metformin (MET), an adenosine monophosphate-activated protein kinase (AMPK) activator, improves progression-free survival of patients with multiple cancers; more than 30 clinical trials are under way to confirm this finding. We postulated that the role of AMPK as a central cellular energy sensor would result in opposite effects on glucose uptake and proliferation, suggesting different roles for (18)F-FDG and 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) in assessing its effectiveness as an antineoplastic agent. METHODS Colon cancer cell lines HT29 (human) and MC26 (murine) were treated for 24 or 72 h with a range of MET concentrations (0-10 mM). Western blotting was used to study the activation of AMPK after MET treatment. Glucose uptake and cell proliferation were measured by cell retention studies with either (18)F-FDG or (18)F-FLT. EdU (ethynyl deoxyuridine, a thymidine analog) and annexin-propidium iodide flow cytometry was performed to determine cell cycle S-phase and apoptotic changes. In vivo (18)F-FDG and (18)F-FLT PET images were acquired before and 24 h after MET treatment of HT29 tumor-bearing mice. RESULTS After 24 h of MET incubation, phosphorylated AMPK levels increased severalfold in both cell lines, whereas total AMPK levels remained unchanged. In cell retention studies, (18)F-FDG uptake increased but (18)F-FLT retention decreased significantly in both cell lines. The numbers of HT29 and MC26 cells in the S phase decreased 36% and 33%, respectively, after MET therapy. Apoptosis increased 10.5-fold and 5.8-fold in HT29 and MC26 cells, respectively, after 72 h of incubation with MET. PET imaging revealed increased (18)F-FDG uptake (mean ± SEM standardized uptake values were 0.71 ± 0.03 before and 1.29 ± 0.11 after MET therapy) (P < 0.05) and decreased (18)F-FLT uptake (mean ± SEM standardized uptake values were 1.18 ± 0.05 before and 0.89 ± 0.01 after MET therapy) (P < 0.05) in HT29 tumor-bearing mice. CONCLUSION MET, through activation of the AMPK pathway, produces a dose-dependent increase in tumor glucose uptake while decreasing cell proliferation in human and murine colon cancer cells. Thus, changes in (18)F-FDG uptake after MET treatment may be misleading. (18)F-FLT imaging is a promising alternative that correlates with the tumor response.
Collapse
Affiliation(s)
- Peiman Habibollahi
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
| | | | | | | | | |
Collapse
|
|
49
|
Massollo M, Marini C, Brignone M, Emionite L, Salani B, Riondato M, Capitanio S, Fiz F, Democrito A, Amaro A, Morbelli S, Piana M, Maggi D, Cilli M, Pfeffer U, Sambuceti G. Metformin temporal and localized effects on gut glucose metabolism assessed using 18F-FDG PET in mice. J Nucl Med 2013; 54:259-66. [PMID: 23287574 DOI: 10.2967/jnumed.112.106666] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
UNLABELLED In the course of metformin treatment, staging abdominal cancer lesions with (18)F-FDG PET images is often hindered by the presence of a high bowel radioactivity. The present study aimed to verify the mechanism underlying this phenomenon. METHODS Fifty-three mice were submitted to dynamic acquisitions of (18)F-FDG kinetics under fasting conditions. Three small-animal PET scans were obtained over a 4-mo study period. The animals were subdivided into 4 groups according to the following metformin administration protocol: group 1, untreated mice (n = 15); group 2, mice exposed to metformin treatment (750 mg/kg/d) for the 48 h before each PET study (pulsed, n = 10); group 3, mice treated for the whole study period (prolonged, n = 10); and group 4, mice in which prolonged treatment was interrupted 48 h before PET (interrupted, n = 8). The rate constant of (18)F-FDG uptake was estimated by Patlak analysis. At the end of the study, the ileum and colon were harvested, washed, and counted ex vivo. Two further groups, of 5 animals each, were included to evaluate the effect of prolonged metformin treatment on phosphorylated adenosine monophosphate (AMP)-activated protein kinase (pAMPK) form and gene expression for thioredoxin-interacting protein (TXNIP). RESULTS Pulsed treatment did not modify gut tracer retention with respect to the untreated group. Conversely, prolonged treatment induced a progressive increase in (18)F-FDG uptake that selectively involved the colonic wall, without any significant contamination of bowel content. This effect persisted after a complete drug washout in the interrupted group. These responses were paralleled by increased pAMPK availability and by reduced expression of TXNIP messenger RNA in colonic enterocytes exposed to prolonged metformin treatment. CONCLUSION Metformin causes a selective increase in colonic (18)F-FDG uptake. This effect appears after a relatively long period of treatment and persists soon after drug washout. Accordingly, the increased bowel glucose metabolism reflects a biologic response to chronic metformin treatment characterized by increased levels of pAMPK and reduced levels of TXNIP.
Collapse
Affiliation(s)
- Michela Massollo
- Nuclear Medicine, Department of Internal Medicine, University of Genoa and IRCCS San Martino-IST, 16132 Genoa, Italy
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
50
|
Lin M, Koo JH, Abi-Hanna D. Management of patients following detection of unsuspected colon lesions by PET imaging. Clin Gastroenterol Hepatol 2011; 9:1025-32. [PMID: 21723237 DOI: 10.1016/j.cgh.2011.06.028] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2011] [Revised: 04/29/2011] [Accepted: 06/14/2011] [Indexed: 12/11/2022]
Abstract
Positron emission tomography (PET) is a well-established and integral component of multimodality imaging in oncology. However, the expanded use of PET in oncological and also non-oncological imaging (such as in assessing inflammatory conditions) has identified more lesions or tumors at unsuspected locations, such as in the large bowel during examination of patients not known to have colorectal disease. We review the clinical significance of colon lesions that were discovered incidentally by PET imaging and management strategies for gastroenterologists.
Collapse
Affiliation(s)
- Michael Lin
- Department of Nuclear Medicine and PET, Liverpool Hospital, University of New South Wales, Liverpool, New SouthWales, Austrailia.
| | | | | |
Collapse
|