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For: Bodei L, Ferone D, Grana CM, Cremonesi M, Signore A, Dierckx RA, Paganelli G. Peptide receptor therapies in neuroendocrine tumors. J Endocrinol Invest 2009;32:360-9. [PMID: 19636207 DOI: 10.1007/bf03345728] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]

For:	Bodei L, Ferone D, Grana CM, Cremonesi M, Signore A, Dierckx RA, Paganelli G. Peptide receptor therapies in neuroendocrine tumors. J Endocrinol Invest 2009;32:360-9. [PMID: 19636207 DOI: 10.1007/bf03345728] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]

Number

Cited by Other Article(s)

Iqbal FM, Rodríguez-Nogales C, Boulens N, Delie F. Formulation and optimization of transferrin-modified genistein nanocrystals: In vitro anti-cancer assessment and pharmacokinetic evaluation. Int J Pharm 2024;667:124863. [PMID: 39447935 DOI: 10.1016/j.ijpharm.2024.124863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 10/01/2024] [Accepted: 10/20/2024] [Indexed: 10/26/2024]

Xu T, Dillon JS, Maluccio MA, Quelle DE, Nash SH, Cho H, Limbach KE, Skill NJ, Bren-Mattison Y, O'Rorke MA. Peptide Receptor Radionuclide Therapy and clinical associations with renal and hematological toxicities and survival in patients with neuroendocrine tumors: an analysis from two U.S. medical centers. J Cancer Res Clin Oncol 2024;150:485. [PMID: 39488644 PMCID: PMC11531437 DOI: 10.1007/s00432-024-06020-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Accepted: 10/26/2024] [Indexed: 11/04/2024]

Abstract

PURPOSE

Renal and hematological toxicity are side effects and dose-limiting factors of Peptide Receptor Radionuclide Therapy (PRRT). We aimed to assess the changes in renal and hematological function and associations with survival in neuroendocrine tumor (NET) patients treated with PRRT.

METHODS

A retrospective cohort of 448 NET patients treated with either 177Lu-DOTATATE or 90Y-DOTATOC were followed for changes of renal and hematological function. Renal function was assessed by monitoring changes in serum creatinine, blood urea nitrogen and estimated glomerular filtration rate. Hematological function was determined by examining changes in white blood cell counts (WBC), platelet counts, and hemoglobin levels over time. Piecewise linear mixed effect models were applied to model the longitudinal repeated measurements of renal and hematological function. Overall survival (OS) and progression-free survival (PFS) were modelled using Cox proportional hazard regressions.

RESULTS

Of the 448 PRRT treated patients, 335 received 177Lu-DOTATATE (74.78%) and 113 were treated with 90Y-DOTATOC (25.22%). Comparing patients treated with 177Lu-DOTATATE to those treated with 90Y-DOTATOC, renal function did not differ significantly prior to, during or after PRRT. Compared with patients treated with 90Y-DOTATOC, significantly decreased indicators of hematological function were observed in those treated with 177Lu-DOTATATE prior to and during PRRT treatment (WBC: estimate, -0.10, 95% CI, -0.15 to -0.05; P < 0.001; platelet count: estimate, -2.53, 95% CI, -3.83 to -1.24; P < 0.001), and no significant recovery was observed in hematological function post PRRT. Individuals who received 177Lu-DOTATATE tended to have a longer PFS (hazard ratio, 0.47, 95%CI: 0.28-0.79, P = 0.004) compared with 90Y-DOTATOC, but there was no difference in OS.

CONCLUSION

There was no significant renal, but minor hematological toxicity, in patients treated with 177Lu-DOTATATE compared with 90Y-DOTATOC. Compared to 90Y-DOTATOC, 177Lu-DOTATATE appears to enhance PFS, but not OS. Treatment with 177Lu-DOTATATE may necessitate follow-up for hematological toxicity irrespective of other therapies prior to PRRT.

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Padmanabhan Nair Sobha R, Jensen CT, Waters R, Calimano-Ramirez LF, Virarkar MK. Appendiceal Neuroendocrine Neoplasms: A Comprehensive Review. J Comput Assist Tomogr 2024;48:545-562. [PMID: 37574653 DOI: 10.1097/rct.0000000000001528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/15/2023]

Abstract

ABSTRACT

Appendiceal neuroendocrine neoplasm (NEN) is the most common adult appendiceal malignant tumor, constituting 16% of gastrointestinal NENs. They are versatile tumors with varying morphology, immunohistochemistry, secretory properties, and cancer genomics. They are slow growing and clinically silent, to begin with, or present with features of nonspecific vague abdominal pain. Most acute presentations are attributed clinically to appendicitis, with most cases detected incidentally on pathology after an appendectomy. Approximately 40% of them present clinically with features of hormonal excess, which is likened to the functional secretory nature of their parent cell of origin. The symptoms of carcinoid syndrome render their presence clinically evident. However, slow growing and symptomatically silent in its initial stages, high-grade neuroendocrine tumors and neuroendocrine carcinomas of the appendix are aggressive and usually have hepatic and lymph node metastasis at presentation. This review article focuses on imaging characteristics, World Health Organization histopathological classification and grading, American Joint Committee on Cancer/Union or International Cancer Control, European Neuroendocrine Tumor Society staging, European Neuroendocrine Tumor Society standardized guidelines for reporting, data interpretation, early-stage management protocols, and advanced-stage appendiceal NENs. Guidelines are also set for the follow-up and reassessment. The role of targeted radiotherapy, chemotherapy, and high-dose somatostatin analogs in treating advanced disease are discussed, along with types of ablative therapies and liver transplantation for tumor recurrence. The search for newer location-specific biomarkers in NEN is also summarized. Regarding the varying aggressiveness of the tumor, there is a scope for research in the field, with plenty of data yet to be discovered.

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Veenstra EB, Brouwers AH, de Groot DJA, Hofland J, Walenkamp AME, Brabander T, Zandee WT, Noordzij W. Comparison of [18F]DOPA and [68Ga]DOTA-TOC as a PET imaging tracer before peptide receptor radionuclide therapy. Eur J Hybrid Imaging 2022;6:12. [PMID: 35701566 PMCID: PMC9198185 DOI: 10.1186/s41824-022-00133-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2022] [Accepted: 03/23/2022] [Indexed: 11/10/2022] Open

Abstract Abstract Background In treatment of neuroendocrine neoplasms (NENs), confirmation of somatostatin receptor expression with 68Ga-DOTA somatostatin analogues is mandatory to determine eligibility for peptide receptor radionuclide therapy (PRRT). [18F]DOPA can detect additional lesions compared to [68Ga]DOTA-TOC. The aim of this study was to explore differences in tumour detection of both tracers and their relevance for selecting patients for PRRT. We retrospectively studied eight patients with NENs who underwent both [68Ga]DOTA-TOC and carbidopa-enhanced [18F]DOPA PET/CT, before first-time PRRT with [177Lu]DOTA-TATE. Tracer order was influenced due to stock availability or to detect suspected metastases with a second tracer. On CT, disease control was defined as a lesion showing complete response, partial response, or stable disease, according to RECIST 1.1. criteria. Results Seven patients with in total 89 lesions completed four infusions of 7.4 GBq [177Lu]DOTA-TATE, one patient received only two cycles. Before treatment, [18F]DOPA PET/CT detected significantly more lesions than [68Ga]DOTA-TOC PET/CT (79 vs. 62, p < .001). After treatment, no difference in number of lesions with disease control was found for [18F]DOPA-only (5/27) and [68Ga]DOTA-TOC-only lesions (4/10, p = .25). [18F]DOPA detected more liver metastases (24/27) compared to [68Ga]DOTA-TOC (7/10, p = .006). Six patients showed inpatient heterogeneity in treatment response between [18F]DOPA-only and [68Ga]DOTA-TOC-only lesions. Conclusions Response to PRRT with [177Lu]DOTA-TATE was comparable for both [68Ga]DOTA-TOC- and [18F]DOPA-only NEN lesions. [18F]DOPA may be capable of predicting response to PRRT while finding more lesions compared to [68Ga]DOTA-TOC, although these additional lesions are often small of size and undetected by diagnostic CT. Collapse

Early Complications of Radioisotope Therapy with Lutetium-177 and Yttrium-90 in Patients with Neuroendocrine Neoplasms-A Preliminary Study. J Clin Med 2022;11:jcm11040919. [PMID: 35207193 PMCID: PMC8874379 DOI: 10.3390/jcm11040919] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 02/06/2022] [Accepted: 02/07/2022] [Indexed: 12/12/2022] Open

Lin AL, Tabar V, Young RJ, Cohen M, Cuaron J, Yang TJ, Rosenblum M, Rudneva VA, Geer EB, Bodei L. Synergism of Checkpoint Inhibitors and Peptide Receptor Radionuclide Therapy in the Treatment of Pituitary Carcinoma. J Endocr Soc 2021;5:bvab133. [PMID: 34466766 PMCID: PMC8402930 DOI: 10.1210/jendso/bvab133] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Indexed: 11/23/2022] Open

Affiliation(s)

Andrew L Lin Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.,Weill Cornell Medical College, New York, New York 10065, USA.,Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.,Multidisciplinary Pituitary and Skull Base Tumor Center, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Viviane Tabar Weill Cornell Medical College, New York, New York 10065, USA.,Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.,Multidisciplinary Pituitary and Skull Base Tumor Center, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Robert J Young Weill Cornell Medical College, New York, New York 10065, USA.,Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Marc Cohen Weill Cornell Medical College, New York, New York 10065, USA.,Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.,Multidisciplinary Pituitary and Skull Base Tumor Center, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.,Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
John Cuaron Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
T Jonathan Yang Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Marc Rosenblum Weill Cornell Medical College, New York, New York 10065, USA.,Multidisciplinary Pituitary and Skull Base Tumor Center, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.,Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Vasilisa A Rudneva Marie-Josée and Henry R. Kravis Center for Molecular Oncology Pathology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Eliza B Geer Weill Cornell Medical College, New York, New York 10065, USA.,Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.,Multidisciplinary Pituitary and Skull Base Tumor Center, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.,Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Lisa Bodei Weill Cornell Medical College, New York, New York 10065, USA.,Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA

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Uccelli L, Boschi A, Cittanti C, Martini P, Panareo S, Tonini E, Nieri A, Urso L, Caracciolo M, Lodi L, Carnevale A, Giganti M, Bartolomei M. ⁹⁰Y/¹⁷⁷Lu-DOTATOC: From Preclinical Studies to Application in Humans. Pharmaceutics 2021;13:1463. [PMID: 34575538 PMCID: PMC8469896 DOI: 10.3390/pharmaceutics13091463] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 08/31/2021] [Accepted: 09/10/2021] [Indexed: 12/30/2022] Open

Affiliation(s)

Licia Uccelli Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (L.U.); (A.C.); (M.G.) Nuclear Medicine Unit, University Hospital, 44124 Ferrara, Italy; (S.P.); (A.N.); (L.U.); (M.C.); (L.L.); (M.B.)
Alessandra Boschi Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy;
Corrado Cittanti Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (L.U.); (A.C.); (M.G.) Nuclear Medicine Unit, University Hospital, 44124 Ferrara, Italy; (S.P.); (A.N.); (L.U.); (M.C.); (L.L.); (M.B.)
Petra Martini Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (L.U.); (A.C.); (M.G.)
Stefano Panareo Nuclear Medicine Unit, University Hospital, 44124 Ferrara, Italy; (S.P.); (A.N.); (L.U.); (M.C.); (L.L.); (M.B.)
Eugenia Tonini Medical Physics Unit, University Hospital, 44124 Ferrara, Italy;
Alberto Nieri Nuclear Medicine Unit, University Hospital, 44124 Ferrara, Italy; (S.P.); (A.N.); (L.U.); (M.C.); (L.L.); (M.B.)
Luca Urso Nuclear Medicine Unit, University Hospital, 44124 Ferrara, Italy; (S.P.); (A.N.); (L.U.); (M.C.); (L.L.); (M.B.)
Matteo Caracciolo Nuclear Medicine Unit, University Hospital, 44124 Ferrara, Italy; (S.P.); (A.N.); (L.U.); (M.C.); (L.L.); (M.B.)
Luca Lodi Nuclear Medicine Unit, University Hospital, 44124 Ferrara, Italy; (S.P.); (A.N.); (L.U.); (M.C.); (L.L.); (M.B.)
Aldo Carnevale Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (L.U.); (A.C.); (M.G.) Radiology Unit, University Hospital, 44124 Ferrara, Italy
Melchiore Giganti Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (L.U.); (A.C.); (M.G.) Radiology Unit, University Hospital, 44124 Ferrara, Italy
Mirco Bartolomei Nuclear Medicine Unit, University Hospital, 44124 Ferrara, Italy; (S.P.); (A.N.); (L.U.); (M.C.); (L.L.); (M.B.)

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Rinzivillo M, Prosperi D, Mazzuca F, Magi L, Iannicelli E, Pilozzi E, Franchi G, Laghi A, Annibale B, Signore A, Panzuto F. [¹⁸F]FDG-PET/CT and long-term responses to everolimus in advanced neuroendocrine neoplasia. J Endocrinol Invest 2021;44:811-818. [PMID: 32767279 DOI: 10.1007/s40618-020-01378-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 07/30/2020] [Indexed: 02/08/2023]

Affiliation(s)

M Rinzivillo Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Via di Grottarossa 1035, 00189, Rome, Italy
D Prosperi Nuclear Medicine Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Rome, Italy
F Mazzuca Medical Oncology Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Rome, Italy Department of Clinical and Molecular Medicine, "Sapienza" University of Rome, Rome, Italy
L Magi Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Via di Grottarossa 1035, 00189, Rome, Italy
E Iannicelli Radiology Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Rome, Italy Department of Medical-Surgical Sciences and of Translational Medicine, "Sapienza" University of Rome, Rome, Italy
E Pilozzi Department of Clinical and Molecular Medicine, "Sapienza" University of Rome, Rome, Italy Pathology Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Rome, Italy
G Franchi Nuclear Medicine Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Rome, Italy
A Laghi Radiology Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Rome, Italy Department of Medical-Surgical Sciences and of Translational Medicine, "Sapienza" University of Rome, Rome, Italy
B Annibale Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Via di Grottarossa 1035, 00189, Rome, Italy Department of Medical-Surgical Sciences and of Translational Medicine, "Sapienza" University of Rome, Rome, Italy
A Signore Nuclear Medicine Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Rome, Italy Department of Medical-Surgical Sciences and of Translational Medicine, "Sapienza" University of Rome, Rome, Italy
F Panzuto Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Via di Grottarossa 1035, 00189, Rome, Italy.

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Zemczak A, Gut P, Pawlak D, Kołodziej M, Królicki L, Kos-Kudła B, Ruchała M, Kamiński G, Kunikowska J. The Safety and Efficacy of the Repeated PRRT with [⁹⁰Y]Y/[¹⁷⁷Lu]Lu-DOTATATE in Patients with NET. Int J Endocrinol 2021;2021:6615511. [PMID: 33552155 PMCID: PMC7847334 DOI: 10.1155/2021/6615511] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Accepted: 01/13/2021] [Indexed: 12/25/2022] Open

Abstract

PURPOSE

The peptide receptor radionuclide therapy (PRRT) is a treatment option for patients with disseminated, inoperable G1 and G2 neuroendocrine tumours (NETs). The study aims to evaluate the safety, efficacy, and progression-free survival (PFS) of patients after retreatment (R-PRRT) and re-retreatment (RR-PRRT) with tandem isotopes [⁹⁰Y]Y/[¹⁷⁷Lu]Lu-DOTATATE. Material and Methods. Out of 99 treated patients with G1 and G2 NETs, 26 were included in the study and treated with the repeated PRRT (with 5 undergoing the re-repeated PRRT treatment) after an initial positive response to four PRRT cycles and later progression of the disease. [⁶⁸Ga]Ga-DOTATATE PET/CT and CT/MRI procedures were performed before and after the treatment. Patients were treated with [⁹⁰Y]Y/[¹⁷⁷Lu]Lu-DOTATATE (1 : 1) with mixed amino acid infusion for kidney protection. Toxicity was evaluated using the CTCAE 3.0 criteria.

RESULTS

The median follow-up was 88 months (the range: 42-164). The median cumulative administered activity was 22.2 GBq (the range: 17.8-30.7 GBq). Myelodysplastic syndrome occurred in one patient (3.8%), and grade 4 renal toxicity was also detected in one patient (3.8%). No other cases of grade 3 or 4 bone marrow and renal toxicity were observed. The median PFS rate was 31 months after the PRRT and 23 months following the R-PRRT. The OS rate from the diagnosis (OS-d) was 109 months and from the start of the PRRT (OS-t)-92.4 months. During the restaging, 3-6 months after the PRRT, PR, SD, and PD were observed in 19.2%, 80.8%, and 0% of the patients, respectively. After the R-PRRT, PR, SD, and PD were observed in 50%, 42.3%, and 7.7% of the patients, respectively.

CONCLUSIONS

The repeated therapy with [⁹⁰Y]Y/[¹⁷⁷Lu]Lu-DOTATATE is safe and effective for patients with disseminated, inoperable G1 and G2 neuroendocrine tumours.

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Shi S, Vissapragada R, Abi Jaoude J, Huang C, Mittal A, Liu E, Zhong J, Kumar V. Evolving role of biomaterials in diagnostic and therapeutic radiation oncology. Bioact Mater 2020;5:233-240. [PMID: 32123777 PMCID: PMC7036731 DOI: 10.1016/j.bioactmat.2020.01.011] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Revised: 01/24/2020] [Accepted: 01/30/2020] [Indexed: 01/11/2023] Open

Briganti V, Cuccurullo V, Berti V, Di Stasio GD, Linguanti F, Mungai F, Mansi L. ^99mTc-EDDA/HYNIC-TOC is a New Opportunity in Neuroendocrine Tumors of the Lung (and in other Malignant and Benign Pulmonary Diseases). Curr Radiopharm 2020;13:166-176. [PMID: 31886756 PMCID: PMC8193811 DOI: 10.2174/1874471013666191230143610] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Revised: 03/11/2019] [Accepted: 11/11/2019] [Indexed: 12/25/2022]

Cuccurullo V, Di Stasio GD, Mansi L. Physiopathological Premises to Nuclear Medicine Imaging of Pancreatic Neuroendocrine Tumours. Curr Radiopharm 2019;12:98-106. [DOI: 10.2174/1874471012666190206094555] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Revised: 02/19/2018] [Accepted: 10/29/2018] [Indexed: 02/07/2023]

Shirota T, Nagakawa Y, Sahara Y, Takishita C, Hijikata Y, Hosokawa Y, Nakajima T, Osakabe H, Katsumata K, Tsuchida A. Surgical resection of neuroendocrine tumors of the pancreas (pNETs) by minimally invasive surgery: the laparoscopic approach. Gland Surg 2018;7:12-19. [PMID: 29629315 DOI: 10.21037/gs.2017.11.06] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]

Ettorre GM, Meniconi RL, Hammel P, Deguelte S, Filippi L, Cianni R. Management of Liver Metastases from Gastroenteropancreatic Neuroendocrine Tumors. Updates Surg 2018. [DOI: 10.1007/978-88-470-3955-1_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]

Lu-177-Based Peptide Receptor Radionuclide Therapy for Advanced Neuroendocrine Tumors. Nucl Med Mol Imaging 2017;52:208-215. [PMID: 29942399 DOI: 10.1007/s13139-017-0505-6] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2017] [Revised: 10/31/2017] [Accepted: 11/01/2017] [Indexed: 10/18/2022] Open

Bodei L, Ćwikla JB, Kidd M, Modlin IM. The role of peptide receptor radionuclide therapy in advanced/metastatic thoracic neuroendocrine tumors. J Thorac Dis 2017;9:S1511-S1523. [PMID: 29201454 DOI: 10.21037/jtd.2017.09.82] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]

Lee ST, Kulkarni HR, Singh A, Baum RP. Theranostics of Neuroendocrine Tumors. Visc Med 2017;33:358-366. [PMID: 29177165 DOI: 10.1159/000480383] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open

Mathur A, Prashant V, Sakhare N, Chakraborty S, Vimalnath K, Mohan RK, Arjun C, Karkhanis B, Seshan R, Basu S, Korde A, Banerjee S, Dash A, Sachdev SS. Bulk Scale Formulation of Therapeutic Doses of Clinical Grade Ready-to-Use 177Lu-DOTA-TATE: The Intricate Radiochemistry Aspects. Cancer Biother Radiopharm 2017. [DOI: 10.1089/cbr.2017.2208] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open

Holmboe S, Hansen PL, Thisgaard H, Block I, Müller C, Langkjær N, Høilund-Carlsen PF, Olsen BB, Mollenhauer J. Evaluation of somatostatin and nucleolin receptors for therapeutic delivery in non-small cell lung cancer stem cells applying the somatostatin-analog DOTATATE and the nucleolin-targeting aptamer AS1411. PLoS One 2017;12:e0178286. [PMID: 28542563 PMCID: PMC5440050 DOI: 10.1371/journal.pone.0178286] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Accepted: 05/10/2017] [Indexed: 01/31/2023] Open

Kulkarni HR, Singh A, Baum RP. Advances in the Diagnosis of Neuroendocrine Neoplasms. Semin Nucl Med 2017;46:395-404. [PMID: 27553465 DOI: 10.1053/j.semnuclmed.2016.06.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]

Targeted Radionuclide Therapy: An Evolution Toward Precision Cancer Treatment. AJR Am J Roentgenol 2017;209:277-288. [PMID: 28463538 DOI: 10.2214/ajr.17.18264] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]

Medina-Ornelas S, García-Pérez F. Effectiveness of radiolabelled somatostatin analogs ( 90 Y-DOTATOC and 177 Lu-DOTATATE) in patients with metastatic neuroendocrine tumors: A single center experience in Mexico. Rev Esp Med Nucl Imagen Mol 2017. [DOI: 10.1016/j.remnie.2017.01.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]

Cavalcoli F, Rausa E, Conte D, Nicolini AF, Massironi S. Is there still a role for the hepatic locoregional treatment of metastatic neuroendocrine tumors in the era of systemic targeted therapies? World J Gastroenterol 2017;23:2640-2650. [PMID: 28487601 PMCID: PMC5403743 DOI: 10.3748/wjg.v23.i15.2640] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2017] [Revised: 03/11/2017] [Accepted: 03/20/2017] [Indexed: 02/06/2023] Open

Bodei L, Kwekkeboom DJ, Kidd M, Modlin IM, Krenning EP. Radiolabeled Somatostatin Analogue Therapy Of Gastroenteropancreatic Cancer. Semin Nucl Med 2016;46:225-38. [PMID: 27067503 DOI: 10.1053/j.semnuclmed.2015.12.003] [Citation(s) in RCA: 73] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]

Medina-Ornelas SS, García-Pérez FO. Effectiveness of radiolabelled somatostatin analogues (⁹⁰Y-DOTATOC and ¹⁷⁷Lu-DOTATATE) in patients with metastatic neuroendocrine tumours: a single centre experience in Mexico. Rev Esp Med Nucl Imagen Mol 2016;36:166-174. [PMID: 27890514 DOI: 10.1016/j.remn.2016.09.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Revised: 09/08/2016] [Accepted: 09/17/2016] [Indexed: 11/26/2022]

Bodei L, Modlin IM, Luster M, Forrer F, Cremonesi M, Hicks RJ, Ezziddin S, Kidd M, Chiti A. Myeloid neoplasms after chemotherapy and PRRT: myth and reality. Endocr Relat Cancer 2016;23:C1-7. [PMID: 27353035 DOI: 10.1530/erc-16-0258] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Accepted: 06/27/2016] [Indexed: 12/14/2022]

Yeong CH, Cheng MH, Ng KH. Therapeutic radionuclides in nuclear medicine: current and future prospects. J Zhejiang Univ Sci B 2015;15:845-63. [PMID: 25294374 DOI: 10.1631/jzus.b1400131] [Citation(s) in RCA: 90] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]

Mariniello A, Bodei L, Tinelli C, Baio SM, Gilardi L, Colandrea M, Papi S, Valmadre G, Fazio N, Galetta D, Paganelli G, Grana CM. Long-term results of PRRT in advanced bronchopulmonary carcinoid. Eur J Nucl Med Mol Imaging 2015;43:441-52. [PMID: 26392198 DOI: 10.1007/s00259-015-3190-7] [Citation(s) in RCA: 87] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2015] [Accepted: 09/04/2015] [Indexed: 11/30/2022]

Abstract

PURPOSE

Peptide receptor radionuclide therapy (PRRT) for the treatment of neuroendocrine tumours (NET) has been explored for almost two decades, but there are still few trials that have exclusively investigated well-differentiated and moderately differentiated NET arising from the respiratory tree. Thus, the aim of this study was to explore the outcome in patients affected by bronchopulmonary carcinoid (BPC) following PRRT.

METHODS

We retrospectively analysed 114 patients with advanced stage BPC consecutively treated with PRRT at the European Institute of Oncology, Milan, from 1997 to 2012 and followed until October 2014. The objective responses, overall survival (OS) and progression-free survival (PFS) were rated, and three different PRRT protocols ((90)Y-DOTATOC vs. (177)Lu-DOTATATE vs. (90)Y-DOTATOC + (177)Lu-DOTATATE) were compared with regard to their efficacy and tolerability.

RESULTS

The median OS (evaluated in 94 of the 114 patients) was 58.8 months. The median PFS was 28.0 months. The (177)Lu-DOTATATE protocol resulted in the highest 5-year OS (61.4%). Morphological responses (partial responses + minor responses) were obtained in 26.5% of the cohort and were associated with longer OS and PFS. The (90)Y-DOTATOC + (177)Lu-DOTATATE protocol provided the highest response rate (38.1%). Adverse events were mild in the majority of patients. However, haematological toxicity negatively affected survival. No severe (grade 3/4) serum creatinine increase was observed. Patients treated with (90)Y-DOTATOC alone more frequently showed a mild/moderate decrease in renal function. In patients treated with chemotherapy before PRRT had a shorter OS and PFS, and a higher risk of developing nephrotoxicity.

CONCLUSION

In a large cohort of patients with advanced BPC treated in a "real-world" scenario and followed up for a median of 45.1 months (range 2-191 months), PRRT proved to be promising in prolonging survival and delaying disease progression. Despite the potential selection biases, considering the risk-benefit ratio, (177)Lu-DOTATATE monotherapy seems the best option for PRRT. Our results indicate that the use of PRRT in earlier stages of the disease could provide a more favorable outcome.

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Alavi M, Omidvari S, Mehdizadeh A, Jalilian AR, Bahrami-Samani A. Metastatic Bone Pain Palliation using (177)Lu-Ethylenediaminetetramethylene Phosphonic Acid. World J Nucl Med 2015;14:109-15. [PMID: 26097421 PMCID: PMC4455166 DOI: 10.4103/1450-1147.157124] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open

Abstract

¹⁷⁷Lu-ethylenediaminetetramethylene phosphonic acid (EDTMP) is presently suggested as an excellent bone seeking radionuclide for developing metastatic bone pain (MBP) palliation agent owing to its suitable nuclear decay characteristics. To find the exact dosage and its efficiency, this clinical study was performed on the human being, using ¹⁷⁷Lu-EDTMP for MBP palliation. ¹⁷⁷Lu-EDTMP was prepared by Iran, atomic energy organization. Thirty consecutive patients with determined tumors, incontrollable MBP, and positive bone scan at 4 weeks before the beginning of the study participated in this study in the nuclear medicine ward. ¹⁷⁷Lu-EDTMP in the form of sterile slow IV injection was administered with a dose of 29.6 MBq/kg. Short form of brief pain inventory questionnaire was used to evaluate the efficiency of the intervention. Questionnaires were filled out by an expert nuclear physician every 2 weeks while the cell blood count was also checked every 2 weeks up to 12 weeks for evaluation of bone marrow suppression and hematological toxicity. Furthermore, whole body scan was done at days 1, 3, and 7. Twenty-five patients showed a significant pain relief since 2 weeks after the injection, and continued until the end of the follow up period (12 weeks). There were no significant early complications such as bone marrow suppression, hematological toxicity, and no systemic adverse effects. No complication was observed in renal function. Twenty one patients showed flare phenomenon that was started after the 12.2 ± 1.78 h lasting for 38.4 ± 23.08. Sixteen patients (53%) were completely treated; nine patients (30%) showed a partial response, and five patients (17%) had no response to treatment. Total response to treatment was achieved in 25 patients (83%). At the end of the evaluation, no bone marrow suppression or hematologic toxicity was observed. ¹⁷⁷Lu-EDTMP has shown suitable physical and biological properties with good results in long term bone pain relief for patients with bone metastasis.

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Zolghadri S, Yousefnia H, Jalilian AR, Fazaeli Y. Production, quality control, biodistribution assessment and preliminary dose evaluation of [177Lu]-tetra phenyl porphyrin complex as a possible therapeutic agent. BRAZ J PHARM SCI 2015. [DOI: 10.1590/s1984-82502015000200011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open

Baum RP, Puranik AD, Kulkarni HR. Peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors: current state and future perspectives. INTERNATIONAL JOURNAL OF ENDOCRINE ONCOLOGY 2015. [DOI: 10.2217/ije.15.5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open

Bodei L, Cremonesi M, Paganelli G. Yttrium-based therapy for neuroendocrine tumors. PET Clin 2015;9:71-82. [PMID: 25029936 DOI: 10.1016/j.cpet.2013.10.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]

Bodei L, Kidd M, Paganelli G, Grana CM, Drozdov I, Cremonesi M, Lepensky C, Kwekkeboom DJ, Baum RP, Krenning EP, Modlin IM. Long-term tolerability of PRRT in 807 patients with neuroendocrine tumours: the value and limitations of clinical factors. Eur J Nucl Med Mol Imaging 2014;42:5-19. [PMID: 25273832 DOI: 10.1007/s00259-014-2893-5] [Citation(s) in RCA: 313] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2014] [Accepted: 08/07/2014] [Indexed: 12/21/2022]

Abstract

PURPOSE

Peptide receptor radionuclide therapy (PRRT) with (90)Y and (177)Lu provides objective responses in neuroendocrine tumours, and is well tolerated with moderate toxicity. We aimed to identify clinical parameters predictive of long-term renal and haematological toxicity (myelodysplastic syndrome and acute leukaemia).

METHODS

Of 807 patients studied at IEO-Milan (1997-2013), 793 (98 %) received (177)Lu (278, 34.4 %), (90)Y (358, 44.4 %) or (177)Lu and (90)Y combined (157. 19.5 %), and 14 (2 %) received combinations of PRRT and other agents. Follow-up was 30 months (1-180 months). The parameters evaluated included renal risk factors, bone marrow toxicity and PRRT features. Data analysis included multiple regression, random forest feature selection, and recursive partitioning and regression trees.

RESULTS

Treatment with (90)Y and (90)Y + (177)Lu was more likely to result in nephrotoxicity than treatment with (177)Lu alone (33.6 %, 25.5 % and 13.4 % of patients, respectively; p < 0.0001). Nephrotoxicity (any grade), transient and persistent, occurred in 279 patients (34.6 %) and was severe (grade 3 + 4) in 12 (1.5 %). In only 20-27 % of any nephrotoxicity was the disease modelled by risk factors and codependent associations (p < 0.0001). Hypertension and haemoglobin toxicity were the most relevant factors. Persistent toxicity occurred in 197 patients (24.3 %). In only 22-34 % of affected patients was the disease modelled by the clinical data (p < 0.0001). Hypertension (regression coefficient 0.14, p < 0.0001) and haemoglobin toxicity (regression coefficient 0.21, p < 0.0001) were pertinent factors. Persistent toxicity was associated with shorter PRRT duration from the first to the last cycle (mean 387 vs. 658 days, p < 0.004). Myelodysplastic syndrome occurred in 2.35 % of patients (modelled by the clinical data in 30 %, p < 0.0001). Platelet toxicity grade (2.05 ± 1.2 vs. 0.58 ± 0.8, p < 0.0001) and longer PRRT duration (22.6 ± 24 vs. 15.5 ± 9 months, p = 0.01) were relevant. Acute leukaemia occurred in 1.1 % of patients (modelled by the clinical data in 18 %, p < 0.0001).

CONCLUSION

Identified risk factors provide a limited (<30 %) risk estimate even with target tissue dosimetry. These data strongly suggest the existence of unidentified individual susceptibilities to radiation-associated disease.

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Yousefnia H, Jalilian AR, Zolghadri S. Preparation and evaluation of Lu-(177) phytate Complex for Radiosynovectomy. World J Nucl Med 2014;13:22-7. [PMID: 25191108 PMCID: PMC4149764 DOI: 10.4103/1450-1147.138570] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open

Galli F, Manni I, Piaggio G, Balogh L, Weintraub BD, Szkudlinski MW, Fremont V, Dierckx RA, Signore A. (99m)Tc-labeled-rhTSH analogue (TR1401) for imaging poorly differentiated metastatic thyroid cancer. Thyroid 2014;24:1297-308. [PMID: 24801227 PMCID: PMC4106381 DOI: 10.1089/thy.2013.0429] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]

Abstract

BACKGROUND

Differentiated thyroid carcinomas originating from thyroid follicular cells are frequent tumors of the thyroid with relatively good prognosis due to improved surgical techniques and follow-up procedures. Poorly differentiated thyroid cancers, which lose iodine uptake ability, in most cases still express thyrotropin (TSH) receptors (TSHR). Therefore, the aim of this study was to radiolabel a superagonist recombinant human TSH (rhTSH) analogue for imaging poorly differentiated thyroid cancer.

METHODS

The TSHR superagonist, TR1401, was labeled with (99m)Tc using an indirect method via succinimidyl-6-hydrazinonicotinate hydrochloride conjugation. In vitro quality controls included SDS-PAGE, cysteine challenge, and cell-binding assay on TSHR positive cell lines (JP09 and ML-1). In vivo studies included tumor targeting experiments in athymic nude CD-1 mice xenografted with several different TSHR positive cells (JP09, K1, and ML-1) and TSHR negative cells (JP02) as control.

RESULTS

The superagonist rhTSH analogue TR1401 was labeled with high labeling efficiency (>95%) and high specific activity (9250 MBq/mg). The labeled molecule retained its biologic activity and structural integrity. In tumor targeting experiments, a focal uptake of radiolabeled TR1401 was observed in TSHR positive cells but not in TSHR negative cells. The same observation was made in a dog with spontaneous intraglandular thyroid cancer.

CONCLUSIONS

We were able to radiolabel the rhTSH superagonist analogue TR1401 with (99m)Tc efficiently with retention of in vitro and in vivo binding capacity to TSHR. The relative role of such novel radiopharmaceutical versus (131)I scanning of thyroid cancer will require future histopathologic and clinical studies, but it may open new perspectives for presurgical staging of thyroid cancer, and diagnosis of radioiodine negative local relapses and/or distant metastases.

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The future of nuclear medicine imaging of neuroendocrine tumors: on a clear day one might see forever…. Eur J Nucl Med Mol Imaging 2014;41:2189-93. [DOI: 10.1007/s00259-014-2836-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]

Zhou G, Sinnett-Smith J, Liu SH, Yu J, Wu J, Sanchez R, Pandol SJ, Abrol R, Nemunaitis J, Rozengurt E, Brunicardi FC. Down-regulation of pancreatic and duodenal homeobox-1 by somatostatin receptor subtype 5: a novel mechanism for inhibition of cellular proliferation and insulin secretion by somatostatin. Front Physiol 2014;5:226. [PMID: 25009500 PMCID: PMC4069483 DOI: 10.3389/fphys.2014.00226] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2014] [Accepted: 05/31/2014] [Indexed: 01/29/2023] Open

Affiliation(s)

Guisheng Zhou Division of General Surgery, Department of Surgery, David Geffen School of Medicine at University of California Los Angeles, CA, USA ; CURE: Digestive Disease Research Center, David Geffen School of Medicine at University of California Los Angeles, CA, USA
Jim Sinnett-Smith CURE: Digestive Disease Research Center, David Geffen School of Medicine at University of California Los Angeles, CA, USA ; Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, CA, USA
Shi-He Liu Division of General Surgery, Department of Surgery, David Geffen School of Medicine at University of California Los Angeles, CA, USA
Juehua Yu Division of General Surgery, Department of Surgery, David Geffen School of Medicine at University of California Los Angeles, CA, USA
James Wu Division of General Surgery, Department of Surgery, David Geffen School of Medicine at University of California Los Angeles, CA, USA
Robbi Sanchez Division of General Surgery, Department of Surgery, David Geffen School of Medicine at University of California Los Angeles, CA, USA
Stephen J Pandol CURE: Digestive Disease Research Center, David Geffen School of Medicine at University of California Los Angeles, CA, USA ; Department of Medicine at Cedars Sinai Medical Center Los Angeles, CA, USA ; Veterans Affairs Los Angeles, CA, USA
Ravinder Abrol Materials and Process Simulation Center, California Institute of Technology Pasadena, CA, USA
John Nemunaitis Gradalis, Inc., Dallas, TX, USA ; Mary Crowley Cancer Research Centers Dallas, TX, USA
Enrique Rozengurt CURE: Digestive Disease Research Center, David Geffen School of Medicine at University of California Los Angeles, CA, USA ; Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, CA, USA
F Charles Brunicardi Division of General Surgery, Department of Surgery, David Geffen School of Medicine at University of California Los Angeles, CA, USA ; CURE: Digestive Disease Research Center, David Geffen School of Medicine at University of California Los Angeles, CA, USA

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Bodei L, Cremonesi M, Kidd M, Grana CM, Severi S, Modlin IM, Paganelli G. Peptide receptor radionuclide therapy for advanced neuroendocrine tumors. Thorac Surg Clin 2014;24:333-49. [PMID: 25065935 DOI: 10.1016/j.thorsurg.2014.04.005] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]

Prasad V, Bodei L, Kidd M, Modlin IM. Whither peptide receptor radionuclide therapy for neuroendocrine tumors: an Einsteinian view of the facts and myths. Eur J Nucl Med Mol Imaging 2014;41:1825-30. [DOI: 10.1007/s00259-014-2780-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]

Barbieri F, Albertelli M, Grillo F, Mohamed A, Saveanu A, Barlier A, Ferone D, Florio T. Neuroendocrine tumors: insights into innovative therapeutic options and rational development of targeted therapies. Drug Discov Today 2014;19:458-68. [DOI: 10.1016/j.drudis.2013.10.015] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2013] [Revised: 09/02/2013] [Accepted: 10/21/2013] [Indexed: 02/07/2023]

Das T, Bhadwal M, Banerjee S, Sarma HD, Shinto A, Kamaleshwaran KK. Preparation of DOTA-TATE and DOTA-NOC freeze-dried kits for formulation of patient doses of 177Lu-labeled agents and their comparison for peptide receptor radionuclide therapy application. J Radioanal Nucl Chem 2014. [DOI: 10.1007/s10967-013-2894-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]

Öksüz MÖ, Winter L, Pfannenberg C, Reischl G, Müssig K, Bares R, Dittmann H. Peptide receptor radionuclide therapy of neuroendocrine tumors with (90)Y-DOTATOC: is treatment response predictable by pre-therapeutic uptake of (68)Ga-DOTATOC? Diagn Interv Imaging 2013;95:289-300. [PMID: 24034971 DOI: 10.1016/j.diii.2013.07.006] [Citation(s) in RCA: 85] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]

Abstract

PURPOSE

PET with (68)Ga-DOTATOC allows for imaging and quantitative assessment of somatostatin receptor expression in neuroendocrine tumors (NET). The aim of this retrospective study was to analyze whether pre-therapeutic (68)Ga-DOTATOC PET/CT is able to predict response to Peptide Receptor Radionuclide Therapy (PRRT).

PATIENTS AND METHODS

Forty patients with advanced stage NET were treated with a fixed dose of (90)Y-DOTATOC (5550 or 3700MBq). Prior to PRRT, each patient received (68)Ga-DOTATOC PET/CT. Treatment results were evaluated after 3months by CT, tumor marker levels and clinical course and correlated with (68)Ga-DOTATOC uptake (SUVmax) and the assumed uptake of (90)Y-DOTATOC in tumor manifestations (MBq/g). ROC analysis and pairwise comparison of area under the curve (AUC) were performed with pre-treatment uptake of (68)Ga-DOTATOC, assumed uptake of (90)Y-DOTATOC and treatment activity alone and in relation to body weight as continuous variables, and response/no response as classification variable.

RESULTS

According to conventional criteria (tumor shrinkage, decrease of tumor markers, improved or stable clinical condition), 20 patients were classified as responders, 16 as non-responders and in four patients findings were equivocal. Using a SUV more than 17.9 as cut-off for favorable outcome, PET was able to predict treatment response of all responders and 15 out of 16 non-responders. All four patients with equivocal findings showed SUV less than or equal to 17.9 and soon experienced tumor progression. The assumed uptake of (90)Y-DOTATOC in tumor manifestations using a cut-off more than 1.26MBq/g as predictor of response was able to correctly classify 19 out of 20 responders, and 14 out of 16 non-responders. In all patients with equivocal findings, the assumed uptake of (90)Y-DOTATOC was below 1.26MBq/g.

CONCLUSION

Pre-therapeutic (68)Ga-DOTATOC tumor uptake as well as assumed uptake of (90)Y-DOTATOC are strongly associated with the results of subsequent PRRT. The defined cut-off values should be confirmed by prospective studies and may then provide the rationale for individual dosing and selecting patients with high likelihood of favorable treatment outcome.

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Naswa N, Bal CS. Divergent role of (68)Ga-labeled somatostatin analogs in the workup of patients with NETs: AIIMS experience. Recent Results Cancer Res 2013;194:321-51. [PMID: 22918767 DOI: 10.1007/978-3-642-27994-2_17] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]

Zaknun JJ, Bodei L, Mueller-Brand J, Pavel ME, Baum RP, Hörsch D, O’Dorisio MS, O’Dorisiol TM, Howe JR, Cremonesi M, Kwekkeboom DJ. The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2013;40:800-16. [PMID: 23389427 PMCID: PMC3622744 DOI: 10.1007/s00259-012-2330-6] [Citation(s) in RCA: 522] [Impact Index Per Article: 43.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]

Abstract

Peptide receptor radionuclide therapy (PRRNT) is a molecularly targeted radiation therapy involving the systemic administration of a radiolabelled peptide designed to target with high affinity and specificity receptors overexpressed on tumours. PRRNT employing the radiotagged somatostatin receptor agonists (90)Y-DOTATOC ([(90)Y-DOTA(0),Tyr(3)]-octreotide) or (177)Lu-DOTATATE ([(177)Lu-DOTA(0),Tyr(3),Thr(8)]-octreotide or [(177)Lu-DOTA(0),Tyr(3)]-octreotate) have been successfully used for the past 15 years to target metastatic or inoperable neuroendocrine tumours expressing the somatostatin receptor subtype 2. Accumulated evidence from clinical experience indicates that these tumours can be subjected to a high absorbed dose which leads to partial or complete objective responses in up to 30 % of treated patients. Survival analyses indicate that patients presenting with high tumour receptor expression at study entry and receiving (177)Lu-DOTATATE or (90)Y-DOTATOC treatment show significantly higher objective responses, leading to longer survival and improved quality of life. Side effects of PRRNT are typically seen in the kidneys and bone marrow. These, however, are usually mild provided adequate protective measures are undertaken. Despite the large body of evidence regarding efficacy and clinical safety, PRRNT is still considered an investigational treatment and its implementation must comply with national legislation, and ethical guidelines concerning human therapeutic investigations. This guidance was formulated based on recent literature and leading experts' opinions. It covers the rationale, indications and contraindications for PRRNT, assessment of treatment response and patient follow-up. This document is aimed at guiding nuclear medicine specialists in selecting likely candidates to receive PRRNT and to deliver the treatment in a safe and effective manner. This document is largely based on the book published through a joint international effort under the auspices of the Nuclear Medicine Section of the International Atomic Energy Agency.

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Bailey DL, Willowson KP. An evidence-based review of quantitative SPECT imaging and potential clinical applications. J Nucl Med 2013;54:83-9. [PMID: 23283563 DOI: 10.2967/jnumed.112.111476] [Citation(s) in RCA: 257] [Impact Index Per Article: 21.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open

Brader P, Serganova I, Blasberg RG. Noninvasive Molecular Imaging Using Reporter Genes. J Nucl Med 2013;54:167-72. [DOI: 10.2967/jnumed.111.099788] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open

Trejtnar F, Laznickova A, Laznicek M, Novy Z, Maina T, Nock BA, Behe M. Distribution, elimination, and renal handling of (99m)technetium-Demogastrin 1. Cancer Biother Radiopharm 2012;27:169-74. [PMID: 22409267 DOI: 10.1089/cbr.2011.1008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open

Radiolabeled somatostatin analogues therapy in advanced neuroendocrine tumors: a single centre experience. JOURNAL OF ONCOLOGY 2012;2012:320198. [PMID: 22934111 PMCID: PMC3425839 DOI: 10.1155/2012/320198] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/30/2012] [Revised: 06/25/2012] [Accepted: 06/26/2012] [Indexed: 12/14/2022]

Bodei L, Cremonesi M, Grana CM, Chinol M, Baio SM, Severi S, Paganelli G. Yttrium-labelled peptides for therapy of NET. Eur J Nucl Med Mol Imaging 2012;39 Suppl 1:S93-102. [PMID: 22388625 DOI: 10.1007/s00259-011-2002-y] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]

Zhou G, Liu SH, Shahi KM, Wang H, Duan X, Lin X, Feng XH, Li M, Fisher WE, Demayo FJ, Dawson D, Brunicardi FC. Negative regulation of pancreatic and duodenal homeobox-1 by somatostatin receptor subtype 5. Mol Endocrinol 2012;26:1225-34. [PMID: 22669743 DOI: 10.1210/me.2012-1095] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open

Abstract

Somatostatin receptor subtype 5 (SSTR5) mediates the inhibitory effect of somatostatin and its analogs on insulin expression/secretion and islet cell proliferation. We provide biochemical and genetic evidence that SSTR5 exerted its physiological actions via down-regulating pancreatic and duodenal homeobox-1 (PDX-1), a β-cell-specific homeodomain-containing transcription factor. Cotransfection of SSTR5 with PDX-1 resulted in dose-dependent inhibition of PDX-1 expression in human embryonic kidney 293 cells. SSTR5 agonist RPL-1980 inhibited PDX-1 expression and abolished glucagon-like peptide 1-stimulated PDX-1 expression in mouse insulinoma β-TC-6 cells. SSTR5 knockdown by short hairpin RNA led to increased PDX-1 expression that was accompanied by enhanced insulin secretion stimulated by high glucose in β-TC6 cells and alternated expressions of cell cycle proteins that favor cell proliferation in mouse insulinoma MIN6 cells. Quantitative RT-PCR analysis showed that cotransfected SSTR5 inhibited PDX-1 mRNA expression, whereas knockdown of SSTR5 increased PDX-1 mRNA expression. In addition, we found that cotransfected wild-type SSTR5 increased PDX-1 ubiquitination in human embryonic kidney 293 cells, whereas SSTR5 P335L, a hypofunctional single nucleotide polymorphism of SSTR5, inhibited PDX-1 ubiquitination. SSTR5 knockout resulted in increased expression of PDX-1, insulin, and proliferating cell nuclear antigen in the islets of sstr(-/-) mice. Immunohistochemistry analysis showed that SSTR5 P335L was associated with elevated expression of PDX-1 in human pancreatic neuroendocrine tumor. Taken together, our studies demonstrated that SSTR5 is a negative regulator for PDX-1 expression and that SSTR5 may mediate the inhibitory effects of somatostatin and its analogs on insulin expression/secretion and cell proliferation via down-regulating PDX-1 at both transcriptional and posttranslational levels.

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