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Willink CY, Jenniskens SFM, Klaassen NJM, Stommel MWJ, van Laarhoven CJHM, Fütterer JJ, Nijsen JFW. Development of an Intratumoral Holmium Microsphere Injection Method in Ex Vivo Human Pancreatic Ductal Adenocarcinoma: A Preclinical Feasibility Study. Cancers (Basel) 2025; 17:1028. [PMID: 40149361 PMCID: PMC11941289 DOI: 10.3390/cancers17061028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Revised: 03/14/2025] [Accepted: 03/17/2025] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND/OBJECTIVES Patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) have a poor prognosis. Local therapy may enhance tumor control and increase resectability. Intratumoral injection of radioactive holmium-166 microspheres presents a promising and minimally invasive treatment with multimodality imaging capabilities (SPECT, CT, MRI). However, holmium-166 microspheres are not commonly used for intratumoral injections, and PDAC is notorious for its high intratumoral pressure. This study developed an intratumoral injection method with nonradioactive holmium-165 microspheres in ex vivo human PDAC specimens using a novel injection system for suspension homogenization. METHODS An injection system was developed and validated in a laboratory setting. Thereafter, intratumoral injections in surgically removed ex vivo PDACs were performed, and parameters were established to optimize feasibility, defined by the ability to inject and control the microsphere distribution. Also, injection limitations and cutoff values were determined. The distribution was assessed by visual confirmation, CT, MRI, ultrasound, and histopathology. RESULTS With a validated injection system, intratumoral injections were performed in ten ex vivo PDAC samples. Feasible injection guidelines include but are not limited to ultrasound or CT needle guidance, a maximum injection volume of <20.0% from the tumor volume, ≤3 needle positions, and an injection volume of 0.3-1.0 mL per needle position. CONCLUSIONS Intratumoral injection of holmium-165 microspheres in ex vivo pancreatic ductal adenocarcinoma was feasible with adherence to injection parameters necessary for effective intratumoral deposition and minimal leakage. The injection system and parameters developed here provide a foundation for future studies on holmium-166 microsphere injections in pancreatic cancer patients, with the aim to improve local tumor control as a part of a multimodal therapy.
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Affiliation(s)
- Coen Ysbrand Willink
- Department of Medical Imaging, Radboud University Medical Center, Geert Grooteplein-Zuid 10, Postbox 9101, 6500 HB Nijmegen, The Netherlands (J.F.W.N.)
| | - Sjoerd Franciscus Maria Jenniskens
- Department of Medical Imaging, Radboud University Medical Center, Geert Grooteplein-Zuid 10, Postbox 9101, 6500 HB Nijmegen, The Netherlands (J.F.W.N.)
| | - Nienke Johanna Maria Klaassen
- Department of Medical Imaging, Radboud University Medical Center, Geert Grooteplein-Zuid 10, Postbox 9101, 6500 HB Nijmegen, The Netherlands (J.F.W.N.)
| | - Martijn Willem Jan Stommel
- Department of Surgery, Radboud University Medical Center, Geert Grooteplein-Zuid 10, Postbox 9101, 6500 HB Nijmegen, The Netherlands
| | | | - Jurgen J. Fütterer
- Department of Medical Imaging, Radboud University Medical Center, Geert Grooteplein-Zuid 10, Postbox 9101, 6500 HB Nijmegen, The Netherlands (J.F.W.N.)
| | - Johannes Frank Wilhelmus Nijsen
- Department of Medical Imaging, Radboud University Medical Center, Geert Grooteplein-Zuid 10, Postbox 9101, 6500 HB Nijmegen, The Netherlands (J.F.W.N.)
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Kauffman N, Singh SK, Morrison J, Zinn KR. Effective therapy with Bismuth-212 labeled macroaggregated albumin in orthotopic mouse breast tumor models. Front Chem 2023; 11:1204872. [PMID: 37234203 PMCID: PMC10206259 DOI: 10.3389/fchem.2023.1204872] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 05/02/2023] [Indexed: 05/27/2023] Open
Abstract
Intravascularly administered radiation therapy using beta (β-)-emitting radioisotopes has relied on either intravenously injected radiolabeled peptides that target cancer or radiolabeled microspheres that are trapped in the tumor following intra-arterial delivery. More recently, targeted intravenous radiopeptide therapies have explored the use of alpha (α)-particle emitting radioisotopes, but microspheres radiolabeled with α-particle emitters have not yet been studied. Here, FDA-approved macroaggregated albumin (MAA) particles were radiolabeled with Bismuth-212 (Bi-212-MAA) and evaluated using clonogenic and survival assays in vitro and using immune-competent mouse models of breast cancer. The in vivo biodistribution of Bi-212-MAA was investigated in Balb/c and C57BL/6 mice with 4T1 and EO771 orthotopic breast tumors, respectively. The same orthotopic breast cancer models were used to evaluate the treatment efficacy of Bi-212-MAA. Our results showed that macroaggregated albumin can be stably radiolabeled with Bi-212 and that Bi-212-MAA can deliver significant radiation therapy to reduce the growth and clonogenic potential of 4T1 and EO771 cells in vitro. Additionally, Bi-212-MAA treatment upregulated γH2AX and cleaved Caspase-3 expression in 4T1 cells. Biodistribution analyses showed 87-93% of the Bi-212-MAA remained in 4T1 and EO771 tumors 2 and 4 h after injection. Following single-tumor treatments with Bi-212-MAA there was a significant reduction in the growth of both 4T1 and EO771 breast tumors over the 18-day monitoring period. Overall, these findings showed that Bi-212-MAA was stably radiolabeled and inhibited breast cancer growth. Bi-212-MAA is an exciting platform to study α-particle therapy and will be easily translatable to larger animal models and human clinical trials.
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Affiliation(s)
- Nathan Kauffman
- Comparative Medicine and Integrative Biology, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, United States
| | - Satyendra Kumar Singh
- Department of Biomedical Engineering, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, United States
| | - James Morrison
- Advanced Radiology Services, Grand Rapids, MI, United States
| | - Kurt R. Zinn
- Departments of Radiology, Biomedical Engineering, Small Animal Clinical Sciences, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, United States
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Willink CY, Jenniskens SFM, Klaassen NJM, Stommel MWJ, Nijsen JFW. Intratumoral injection therapies for locally advanced pancreatic cancer: systematic review. BJS Open 2023; 7:zrad052. [PMID: 37254902 PMCID: PMC10230443 DOI: 10.1093/bjsopen/zrad052] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 03/03/2023] [Accepted: 04/05/2023] [Indexed: 06/01/2023] Open
Abstract
INTRODUCTION Pancreatic cancer has one of the worst prognoses of all cancers. Patients with locally advanced pancreatic cancer have a 12.7-20.2 per cent chance of receiving curative surgery after induction systemic chemotherapy. Intratumoral injection therapies have been studied as complementary treatment options for improved local tumour control. The aim of this systematic review was to provide an overview of intratumoral injection therapies, their safety, and oncological outcome in patients with locally advanced pancreatic cancer. METHODS A literature search was conducted in PubMed, Embase and the Cochrane Library for articles written in English up to 28 November 2022. All study designs involving at least five patients with locally advanced pancreatic cancer who were treated with an intratumoral injection therapy were included. Critical appraisal of the included studies was performed using the Newcastle-Ottawa scale. RESULTS After evaluation of the 1680 articles yielded by the systematic search, 52 studies treating 1843 patients were included. Included intratumoral injection treatment modalities comprised iodine-125 (125I) seed brachytherapy (32 studies, 1283 patients), phosphorus-32 (32P) microbrachytherapy (5 studies, 133 patients), palladium-103 (103Pd) seed brachytherapy (2 studies, 26 patients), immunotherapy (9 studies, 330 patients), and chemotherapy (4 studies, 71 patients). Overall survival ranged between 7.0 and 16.0 months for 125I, 5.2 and 15.5 months for 32P, 6.9 and 10.0 months for 103Pd, 5.8 and 13.8 months for immunotherapy, and 9.0 and 16.2 months for chemotherapy. Severe complication (greater than or equal to grade III complications using Clavien-Dindo classification) rates were 6.2 per cent for 125I, 49.2 per cent for 32P, 15 per cent for 103Pd, 57.9 per cent for immunotherapy, and 0 per cent for chemotherapy. CONCLUSION Five intratumoral injection therapies are described and an overview is reported. Some intratumoral injection therapies for patients with locally advanced pancreatic cancer seem safe, although 32P microbrachytherapy and immunotherapy require additional evidence. Currently available data are insufficient to provide firm conclusions regarding the added value to survival. The potential advantage of intratumoral injection therapies complementary to conventional care should be studied in well designed RCTs.
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Affiliation(s)
- Coen Ysbrand Willink
- Department of Medical Imaging, Radboud Institute for Health Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands
| | | | - Nienke Johanna Maria Klaassen
- Department of Medical Imaging, Radboud Institute for Health Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Martijn Willem Jan Stommel
- Department of Surgery, Radboud Institute for Health Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Johannes Frank Wilhelmus Nijsen
- Department of Medical Imaging, Radboud Institute for Health Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands
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Naidu J, Bartholomeusz D, Zobel J, Safaeian R, Hsieh W, Crouch B, Ho K, Calnan D, Singhal N, Ruszkiewicz A, Chen JW, Tan CP, Dolan P, Nguyen NQ. Combined chemotherapy and endoscopic ultrasound-guided intratumoral 32P implantation for locally advanced pancreatic adenocarcinoma: a pilot study. Endoscopy 2022; 54:75-80. [PMID: 33440437 DOI: 10.1055/a-1353-0941] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND This study evaluated clinical outcomes of combined chemotherapy and endoscopic ultrasound (EUS)-guided intratumoral radioactive phosphorus-32 (32P) implantation in locally advanced pancreatic adenocarcinoma (LAPC). METHODS Consecutive patients with newly diagnosed LAPC were recruited over 20 months. Baseline computed tomography and 18F-2-fluoro-2-deoxy-D-glucose (18FDG) positron emission tomography-computed tomography were performed and repeated after 12 weeks to assess treatment response. Following two cycles of conventional chemotherapy, patients underwent EUS-guided 32P implantation followed by six chemotherapy cycles. RESULTS 12 patients with LAPC (median age 69 years [interquartile range 61.5-73.3]; 8 male) completed treatment. Technical success was 100 % with no procedural complications. At 12 weeks, median reduction in tumor volume was 8.2 cm3 (95 % confidence interval 4.95-10.85; P = 0.003), with minimal or no 18FDG uptake in nine patients (75 %). Tumor downstaging was achieved in six patients (50 %), leading to successful resection in five (42 %), including four R0 resections (80 %). CONCLUSIONS EUS-guided 32P implantation was feasible, well tolerated, and resulted in a 42 % surgical resection rate. Further evaluation in a larger randomized multicenter trial is warranted.
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Affiliation(s)
- Jeevinesh Naidu
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia.,School of Health and Medical Sciences, University of Adelaide, Adelaide, Australia
| | - Dylan Bartholomeusz
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia.,School of Health and Medical Sciences, University of Adelaide, Adelaide, Australia.,Department of Nuclear Medicine, Royal Adelaide Hospital, Adelaide, Australia
| | - Joshua Zobel
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia
| | - Romina Safaeian
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia
| | - William Hsieh
- Department of Nuclear Medicine, Royal Adelaide Hospital, Adelaide, Australia
| | - Benjamin Crouch
- Department of Nuclear Medicine, Royal Adelaide Hospital, Adelaide, Australia
| | - Karen Ho
- Department of Nuclear Medicine, Royal Adelaide Hospital, Adelaide, Australia
| | - Deborah Calnan
- Department of Nuclear Medicine, Royal Adelaide Hospital, Adelaide, Australia
| | - Nimit Singhal
- Department of Medical Oncology, Royal Adelaide Hospital, Adelaide, Australia
| | - Andrew Ruszkiewicz
- School of Health and Medical Sciences, University of Adelaide, Adelaide, Australia.,Department of Pathology, Royal Adelaide Hospital, Adelaide, Australia
| | - John W Chen
- Department of Hepatobiliary Surgery, Royal Adelaide Hospital, Adelaide, Australia
| | - Chuan Ping Tan
- Department of Hepatobiliary Surgery, Royal Adelaide Hospital, Adelaide, Australia
| | - Paul Dolan
- Department of Hepatobiliary Surgery, Royal Adelaide Hospital, Adelaide, Australia
| | - Nam Q Nguyen
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia.,School of Health and Medical Sciences, University of Adelaide, Adelaide, Australia
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Bratanic A, Bozic D, Mestrovic A, Martinovic D, Kumric M, Ticinovic Kurir T, Bozic J. Role of endoscopic ultrasound in anticancer therapy: Current evidence and future perspectives. World J Gastrointest Oncol 2021; 13:1863-1879. [PMID: 35070030 PMCID: PMC8713319 DOI: 10.4251/wjgo.v13.i12.1863] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 05/17/2021] [Accepted: 08/27/2021] [Indexed: 02/06/2023] Open
Abstract
The digestive system is one of the most common sites of malignancies in humans. Since gastrointestinal tumors represent a massive global health burden both in terms of morbidity and health care expenditures, scientists continuously develop novel diagnostic and therapeutic methods to ameliorate the detrimental effects of this group of diseases. Apart from the well-established role of the endoscopic ultrasound (EUS) in the diagnostic course of gastrointestinal and hepatobiliary malignancies, we have recently become acquainted with a vast array of its therapeutic possibilities. A multitude of previously established, evidence-based methods that might now be guided by the EUS emerged: Radiofrequency ablation, brachytherapy, fine needle injection, celiac plexus neurolysis, and endoscopic submucosal dissection. In this review we endeavored to provide a comprehensive overview of the role of these methods in different malignancies of the digestive system, primarily in the treatment and symptom control in pancreatic cancer, and additionally in the management of hepatic, gastrointestinal tumors, and pancreatic cysts.
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Affiliation(s)
- Andre Bratanic
- Department of Gastroenterology and Hepatology, University Hospital of Split, Split 21000, Croatia
| | - Dorotea Bozic
- Department of Gastroenterology and Hepatology, University Hospital of Split, Split 21000, Croatia
| | - Antonio Mestrovic
- Department of Gastroenterology and Hepatology, University Hospital of Split, Split 21000, Croatia
| | - Dinko Martinovic
- Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
| | - Marko Kumric
- Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
| | - Tina Ticinovic Kurir
- Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
- Department of Endocrinology, University Hospital of Split, Split 21000, Croatia
| | - Josko Bozic
- Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
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Abstract
PURPOSE OF REVIEW The aim of this review is to evaluate the emerging role of endoscopic ultrasound (EUS) in the guidance of tumor-targeted therapies for patients with pancreatic cancer (PC). RECENT FINDINGS EUS-guided ablation, brachytherapy, fiducial marker placement, and antitumor agent injection have been described to date. EUS-guided fiducial placement for SBRT in pancreatic cancer has entered the clinical practice and is performed at many centers clinically without a research protocol. EUS-guided brachytherapy and RFA have been shown to be feasible and safe procedures, and potentially offer local disease control. Other potential techniques of EUS-guided treatment of pancreatic cancer are still considered experimental, with many of them appearing to be safe and reasonably well tolerated. However, their effectiveness and exact role in oncological treatment have yet to be established. Clinical trials with many of the techniques/agents described are underway and multicentric randomized trials with prospective design are eagerly awaited.
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Bhutani MS, Klapman JB, Tuli R, El-Haddad G, Hoffe S, Wong FCL, Chasen B, Fogelman DR, Lo SK, Nissen NN, Hendifar AE, Varadhachary G, Katz MHG, Erwin WD, Koay EJ, Tamm EP, Singh BS, Mehta R, Wolff RA, Soman A, Cazacu IM, Herman JM. An open-label, single-arm pilot study of EUS-guided brachytherapy with phosphorus-32 microparticles in combination with gemcitabine +/- nab-paclitaxel in unresectable locally advanced pancreatic cancer (OncoPaC-1): Technical details and study protocol. Endosc Ultrasound 2020; 9:24-30. [PMID: 31670288 PMCID: PMC7038730 DOI: 10.4103/eus.eus_44_19] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Current treatment options for patients with unresectable locally advanced pancreatic cancer (LAPC) include chemotherapy alone or followed by chemoradiation or stereotactic body radiotherapy. However, the prognosis for these patients remains poor, with a median overall survival <12 months. Therefore, novel treatment options are needed. Currently, there is no brachytherapy device approved for pancreatic cancer treatment. Hereby, we present the protocol of a prospective, multicenter, interventional, open-label, single-arm pilot study (OncoPac-1, Clinicaltrial.gov-NCT03076216) aiming to determine the safety and efficacy of Phosphorus-32 when implanted directly into pancreatic tumors using EUS guidance, for patients with unresectable LAPC undergoing chemotherapy (gemcitabine ± nab-paclitaxel).
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Affiliation(s)
- Manoop S Bhutani
- Department of Gastroenterology, Hepatology and Nutrition, Houston, TX, USA
| | - Jason B Klapman
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA
| | - Richard Tuli
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Ghassan El-Haddad
- Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center, Tampa, FL, USA
| | - Sarah Hoffe
- Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL, USA
| | - Franklin C L Wong
- Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Beth Chasen
- Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - David R Fogelman
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Simon K Lo
- Division of Digestive and Liver Diseases, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Nicholas N Nissen
- Department of Surgery, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Andrew E Hendifar
- Department of Hematology/Oncology, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Gauri Varadhachary
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Matthew H G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - William D Erwin
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Eugene J Koay
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Eric P Tamm
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ben S Singh
- Department of Gastroenterology, Hepatology and Nutrition, Houston, TX, USA
| | - Rutika Mehta
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA
| | - Robert A Wolff
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ashish Soman
- Department of OncoSil Medical Ltd., Sydney, Australia
| | - Irina M Cazacu
- Department of Gastroenterology, Hepatology and Nutrition, Houston, TX, USA
| | - Joseph M Herman
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Bakker RC, Lam MG, van Nimwegen SA, Rosenberg AJ, van Es RJ, Nijsen JFW. Intratumoral treatment with radioactive beta-emitting microparticles: a systematic review. JOURNAL OF RADIATION ONCOLOGY 2017; 6:323-341. [PMID: 29213358 PMCID: PMC5700992 DOI: 10.1007/s13566-017-0315-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/21/2017] [Accepted: 05/08/2017] [Indexed: 02/06/2023]
Abstract
PURPOSE The purpose of this study was to review the role of radioactive microparticles (1-100 μm) for the treatment of solid tumors and provide a comprehensive overview of the feasibility, safety, and efficacy. METHODS A systematic search was performed in MEDLINE, EMBASE, and The Cochrane Library (January 2017) by combining synonyms for the determinants "tumor," "injection," and "radionuclide." Data on injection technique, toxicity, tumor response, and survival were collected. RESULTS The search yielded 7271 studies, and 37 were included for analysis. Twelve studies were performed in human patients and 25 animal studies. The studies were heterogeneous in patient population, tumors, follow-up time, and treatment characteristics. The direct intratumoral injection of radioactive microparticles resulted in a response rate of 71% in a variety of tumors and uncomplicated procedures with high cumulative doses of >19,000 Gy were reported. CONCLUSION The large variety of particles, techniques, and treated tumors in the studies provided an important insight into issues concerning efficacy, safety, particle and isotope choice, and other concepts for future research. Animal studies showed efficacy and a dose response. Most studies in humans concluded that intratumoral treatment with radioactive beta-emitting microparticles is relatively safe and effective. Conflicting evidence about safety and efficacy might be explained by the considerable variation in the treatment characteristics. Larger particles had a better retention which resulted in higher anti-tumor effect. Leakage seems to follow the path of least resistance depending on anatomical structures. Subsequently, a grid-like injection procedure with small volume depots is advised over a single large infusion. Controlled image-guided treatment is necessary because inadequate local delivery and inhomogeneous dose distribution result in reduced treatment efficacy and in potential complications.
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Affiliation(s)
- Robbert C. Bakker
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
- Department of Oral and Maxillofacial Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Marnix G.E.H. Lam
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
| | - Sebastiaan A. van Nimwegen
- Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
| | - Antoine J.W.P. Rosenberg
- Department of Oral and Maxillofacial Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Robert J.J. van Es
- Department of Head and Neck Surgical Oncology, UMC Utrecht Cancer Center, Utrecht, The Netherlands
| | - J. Frank W. Nijsen
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
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Xu YP, Yang M. Advancement in treatment and diagnosis of pancreatic cancer with radiopharmaceuticals. World J Gastrointest Oncol 2016; 8:165-172. [PMID: 26909131 PMCID: PMC4753167 DOI: 10.4251/wjgo.v8.i2.165] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 09/30/2015] [Accepted: 12/18/2015] [Indexed: 02/05/2023] Open
Abstract
Pancreatic cancer (PC) is a major health problem. Conventional imaging modalities show limited accuracy for reliable assessment of the tumor. Recent researches suggest that molecular imaging techniques with tracers provide more biologically relevant information and are benefit for the diagnosis of the cancer. In addition, radiopharmaceuticals also play more important roles in treatment of the disease. This review summaries the advancement of the radiolabeled compounds in the theranostics of PC.
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Abstract
Pancreatic cancer is an insidious type of cancer with its symptoms manifested upon extensive disease. The overall 5-year survival rates between 0.4 and 4%. Surgical resection is an option for only 10% of the patients with pancreatic cancer. Local recurrence and hepatic metastases occur within 2 years after surgery. There are currently several molecular pathways investigated and novel targeted treatments are on the market. However; the nature of pancreatic cancer with its ability to spread locally in the primary site and lymph nodes indicates that further experimentation with local interventional therapies could be a future treatment proposal as palliative care or adjunct to gene therapy and chemotherapy/radiotherapy. In the current review, we will summarize the molecular pathways and present the interventional treatment options for pancreatic cancer.
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Gao W, Liu L, Liu ZY, Wang Y, Jiang B, Liu XN. Intratumoral injection of 32P-chromic phosphate in the treatment of implanted pancreatic carcinoma. Cancer Biother Radiopharm 2010; 25:215-24. [PMID: 20423235 DOI: 10.1089/cbr.2008.0596] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
AIM The aim of this study was to observe the biological distribution and anticancer effect of (32)P-chromic phosphate colloid (Cr(32)PO(4), (32)P-CP) after intratumoral injection to Pc-3 human pancreatic carcinoma-bearing nude mice. METHODS Eighty-four (84) BALB/c nude mice with transplanted tumor were allocated to 11 groups. Groups 1-5 (n = 6) were intratumorally injected with 14.8 MBq of (32)P-CP and sacrificed at 2, 24, 48, 72, and 168 hours, respectively. Groups 6-11 (n = 9) received injections of 3.7, 7.4, 14.8, 18.5, 29.6, and 0 MBq of (32)P-CP, respectively, and the tumor volume on body surface was measured daily. The animals (n = 6) were sacrificed at 14 days after administration. The dynamic distribution of radioactivity in body (percentage of injected dose per g), morphological changes, the tumor-inhibiting rate (TIR), proliferating index (PI), proliferating cell nuclear antigen (PCNA) tumor microvascular density (MVD), continuous counting of white blood cells (WBCs) and platelets (PLTs) in venous blood, body weight, and toxic reactions were observed. RESULTS The injected (32)P-CP mainly accumulated in the tumor mass and was retained for a long time. The TIR of each dosage group in order was 21.68%, 39.73%, 50.43%, 71.18%, and 74.09% (F = 159.74; p < 0.001), PI was 70.85, 67.90, 46.70, 20.66, 10.75, and 90.11 (F = 509.54; p < 0.001), and MVD count was 39.19, 28.33, 17.45, 8.89, 8.10, and 64.80 (F = 643.26; p < 0.001), respectively. The data for WBC, PLT, and body weight observed for 28 days in the treatment groups did not indicate significant differences compared with those of the control group. CONCLUSIONS Interstitial injection of (32)P-CP seems to be a safe and effective interventional nuclide therapy for pancreatic carcinoma-bearing nude mice.
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Affiliation(s)
- Wen Gao
- Nuclear Medicine Technology Institution, Clinical Medical College of Southeast University, Nanjing, China
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Injectable intratumoral depot of thermally responsive polypeptide-radionuclide conjugates delays tumor progression in a mouse model. J Control Release 2010; 144:2-9. [PMID: 20117157 DOI: 10.1016/j.jconrel.2010.01.032] [Citation(s) in RCA: 85] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2009] [Accepted: 01/25/2010] [Indexed: 11/22/2022]
Abstract
This study evaluated a biodegradable drug delivery system for local cancer radiotherapy consisting of a thermally sensitive elastin-like polypeptide (ELP) conjugated to a therapeutic radionuclide. Two ELPs (49 kDa) were synthesized using genetic engineering to test the hypothesis that injectable biopolymeric depots can retain radionuclides locally and reduce the growth of tumors. A thermally sensitive polypeptide, ELP(1), was designed to spontaneously undergo a soluble-insoluble phase transition (forming viscous microparticles) between room temperature and body temperature upon intratumoral injection, while ELP(2) was designed to remain soluble upon injection and to serve as a negative control for the effect of aggregate assembly. After intratumoral administration of radionuclide conjugates of ELPs into implanted tumor xenografts in nude mice, their retention within the tumor, spatio-temporal distribution, and therapeutic effect were quantified. The residence time of the radionuclide-ELP(1) in the tumor was significantly longer than the thermally insensitive ELP(2) conjugate. In addition, the thermal transition of ELP(1) significantly protected the conjugated radionuclide from dehalogenation, whereas the conjugated radionuclide on ELP(2) was quickly eliminated from the tumor and cleaved from the biopolymer. These attributes of the thermally sensitive ELP(1) depot improved the antitumor efficacy of iodine-131 compared to the soluble ELP(2) control. This novel injectable and biodegradable depot has the potential to control advanced-stage cancers by reducing the bulk of inoperable tumors, enabling surgical removal of de-bulked tumors, and preserving healthy tissues.
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Rudloff U, Maker AV, Brennan MF, Allen PJ. Randomized Clinical Trials in Pancreatic Adenocarcinoma. Surg Oncol Clin N Am 2010; 19:115-50. [DOI: 10.1016/j.soc.2009.09.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Chang KJ, Irisawa A. EUS 2008 Working Group document: evaluation of EUS-guided injection therapy for tumors. Gastrointest Endosc 2009; 69:S54-S58. [PMID: 19179171 DOI: 10.1016/j.gie.2008.10.057] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2008] [Accepted: 10/28/2008] [Indexed: 02/08/2023]
Affiliation(s)
- Kenneth J Chang
- Comprehensive Digestive Disease Center, University of California, Irvine, USA
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