177Lu-DOTATATE therapy in metastatic/inoperable pheochromocytoma-paraganglioma

Jaiswal, Sanjeet Kumar; Sarathi, Vijaya; Memon, Saba Samad; Garg, Robin; Verma, Priyanka; Shah, Ravikumar; Sehemby, Manjeet Kaur; Patil, Virendra; Jadhav, Swati; Lila, Anurag; Shah, Nalini; Bandgar, Tushar

doi:10.1530/ec-20-0292

Cited by 39 publications

(52 citation statements)

References 24 publications

(39 reference statements)

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“…177 Lu-DOTATATE showed that only one of the 19 patients reviewed with SPECT/CT had progressive disease, while with CT, according to RECIST 1.1, all patients either had stable disease (n=20) or partial response (n=2). The median OS calculated was 49.6 months and median PFS was 21.6 (88); these were not established in other recent studies (87,89,90).…”

Section: Experiences With Peptide Receptor Radionuclide Therapy Usingmentioning

confidence: 74%

“…There were also minimal grade III/IV toxicities reported in patients, which included gastritis in 7, weight loss in 5, flushing in 3, and headaches in 2 ( 128 ). Another study used 225 Ac-DOTATATE as compassionate care in two patients with progressive PCC after 3 cycles of 177 Lu-DOTATATE; however, results on the effectiveness and toxicity were not published ( 89 ).…”

Section: Future Avenues Of Somatostatin-based Therapy In Ppglsmentioning

confidence: 99%

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Somatostatin Receptors and Analogs in Pheochromocytoma and Paraganglioma: Old Players in a New Precision Medicine World

et al. 2021

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Neuroendocrine tumors overexpress somatostatin receptors, which serve as important and unique therapeutic targets for well-differentiated advanced disease. This overexpression is a well-established finding in gastroenteropancreatic neuroendocrine tumors which has guided new medical therapies in the administration of somatostatin analogs, both “cold”, particularly octreotide and lanreotide, and “hot” analogs, chelated to radiolabeled isotopes. The binding of these analogs to somatostatin receptors effectively suppresses excess hormone secretion and tumor cell proliferation, leading to stabilization, and in some cases, tumor shrinkage. Radioisotope-labeled somatostatin analogs are utilized for both tumor localization and peptide radionuclide therapy, with 68Ga-DOTATATE and 177Lu-DOTATATE respectively. Benign and malignant pheochromocytomas and paragangliomas also overexpress somatostatin receptors, irrespective of embryological origin. The pattern of somatostatin receptor overexpression is more prominent in succinate dehydrogenase subunit B gene mutation, which is more aggressive than other subgroups of this disease. While the Food and Drug Administration has approved the use of 68Ga-DOTATATE as a radiopharmaceutical for somatostatin receptor imaging, the use of its radiotherapeutic counterpart still needs approval beyond gastroenteropancreatic neuroendocrine tumors. Thus, patients with pheochromocytoma and paraganglioma, especially those with inoperable or metastatic diseases, depend on the clinical trials of somatostatin analogs. The review summarizes the advances in the utilization of somatostatin receptor for diagnostic and therapeutic approaches in the neuroendocrine tumor subset of pheochromocytoma and paraganglioma; we hope to provide a positive perspective in using these receptors as targets for treatment in this rare condition.

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Section: Experiences With Peptide Receptor Radionuclide Therapy Usingmentioning

confidence: 74%

Section: Future Avenues Of Somatostatin-based Therapy In Ppglsmentioning

confidence: 99%

Somatostatin Receptors and Analogs in Pheochromocytoma and Paraganglioma: Old Players in a New Precision Medicine World

et al. 2021

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“…The more favorable response of PCC to 131 I-MIBG therapy is a promising observation because of the recently reported poorer outcomes in PCC to 177 Lu-PRRT. [ 22 ] However, this finding needs to be viewed with caution and lack of generalizability due to the small sample size between the groups. Large-scale prospective trials are needed to confirm this observation.…”

Section: Discussionmentioning

confidence: 99%

Low-dose, low-specific activity ¹³¹I-metaiodobenzyl guanidine therapy in metastatic pheochromocytoma/sympathetic paraganglioma: Single-center experience from Western India

Barnabas¹,

Jaiswal²,

Memon³

et al. 2021

Indian J Endocr Metab

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Introduction: Radionuclide therapy is a promising treatment modality in metastatic pheochromocytoma/paraganglioma (PPGL). There is scarce data on 131 I-metaiodobenzyl guanidine ( 131 I-MIBG) therapy from the Indian subcontinent. Hence, we aim to study the safety and effectiveness of low-dose, low-specific activity (LSA) 131 I-MIBG therapy in patients with symptomatic, metastatic PPGL. Methods: Clinical, hormonal, and radiological response parameters and side effects of LSA 131 I-MIBG therapy in patients with symptomatic, metastatic PPGL were retrospectively reviewed. World health organizations’ (WHO) symptomatic, hormonal, and tumor response, and response evaluation criteria in solid tumors (RECIST1.1) criteria were used to assess the response. Results: Seventeen (PCC: 11, sympathetic PGL: 06) patients (15 with disease progression) received low-dose LSA 131 I-MIBG therapy. Complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD) were 18% (3/17), 24% (4/17), 18% (3/17), and 41% (7/17), respectively, for WHO symptomatic response; 20% (2/10), 10% (1/10), 30% (3/10), and 40% (4/10), respectively, for WHO hormonal response; and 19% (3/16), 6% (1/16), 31% (5/16), and 44% (7/16), respectively for tumor response based on RECIST1.1. All patients with symptomatic PD and 50% (2/4) with hormonal PD had progression as per RECIST1.1 criteria. Side effects included thrombocytopenia, acute myeloid leukemia, mucoepidermoid carcinoma, and azoospermia in 6% (1/17) each. Conclusions: Our study reaffirms the modest efficacy and safety of low-dose, LSA 131 I-MIBG therapy in patients with symptomatic, metastatic PPGL. Symptomatic, but not hormonal, progression after 131 I-MIBG therapy correlates well with tumor progression and should be further evaluated with imaging. In resource-limited settings, anatomic imaging alone may be used to assess tumor response to 131 I-MIBG therapy.

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“… 23 The agent is under different clinical trials to get approval from respective authorities in different regions of world. 24 - 26 In Pakistan, we have also developed the freeze-dried kit of DOTATATE for imaging and therapy of NETs at affordable cost.…”

Section: Discussionmentioning

confidence: 99%

¹⁷⁷Lu-DOTATATE Peptide Receptor Radionuclide Therapy: Indigenously Developed Freeze Dried Cold Kit and Biological Response in In-Vitro and In-Vivo Models

2021

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Somatostatin receptors (SStR) based 177Lu-DOTATATE therapy is known as one of the highly effective neuroendocrine tumors (NETs) treatment strategy. Development of DOTATATE freeze-dried kit for imaging and therapy of SStR positive NETs is a prime goal in neuroendocrine cancer research. The present work describes the development of 177Lu-DOTATATE freeze dried cold kit for indigenous needs, through technology development fund (TDF) program offered by Higher Education Commission (HEC) Pakistan. The parameters for freeze dried kit production was optimized and tested the stored lyophilized cold kits for different time intervals after labeling with 177Lu radioisotope. The effect of ligand to radionuclide ratio, pH and reaction time at 90°C was recorded. Five times greater molar concentration of ligand, pH 5 and 30 min reaction time were the effective reaction conditions for maximum radiochemical yield. The radiolabeling yield at 1 day, 1-week and 4-week post storing period showed ∼100% radiochemical yield. The biodistribution study using rat model depicted the absence of non-targeted accumulation while glomerular filtration rate also explains the rapid renal washout. Cytotoxicity study showed quite favorable results for subjecting the radiopharmaceutical to clinical practice in Pakistan.

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177Lu-DOTATATE therapy in metastatic/inoperable pheochromocytoma-paraganglioma

Cited by 39 publications

References 24 publications

Somatostatin Receptors and Analogs in Pheochromocytoma and Paraganglioma: Old Players in a New Precision Medicine World

Somatostatin Receptors and Analogs in Pheochromocytoma and Paraganglioma: Old Players in a New Precision Medicine World

Low-dose, low-specific activity ¹³¹I-metaiodobenzyl guanidine therapy in metastatic pheochromocytoma/sympathetic paraganglioma: Single-center experience from Western India

¹⁷⁷Lu-DOTATATE Peptide Receptor Radionuclide Therapy: Indigenously Developed Freeze Dried Cold Kit and Biological Response in In-Vitro and In-Vivo Models

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177Lu-DOTATATE therapy in metastatic/inoperable pheochromocytoma-paraganglioma

Cited by 39 publications

References 24 publications

Somatostatin Receptors and Analogs in Pheochromocytoma and Paraganglioma: Old Players in a New Precision Medicine World

Somatostatin Receptors and Analogs in Pheochromocytoma and Paraganglioma: Old Players in a New Precision Medicine World

Low-dose, low-specific activity 131I-metaiodobenzyl guanidine therapy in metastatic pheochromocytoma/sympathetic paraganglioma: Single-center experience from Western India

177Lu-DOTATATE Peptide Receptor Radionuclide Therapy: Indigenously Developed Freeze Dried Cold Kit and Biological Response in In-Vitro and In-Vivo Models

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Low-dose, low-specific activity ¹³¹I-metaiodobenzyl guanidine therapy in metastatic pheochromocytoma/sympathetic paraganglioma: Single-center experience from Western India

¹⁷⁷Lu-DOTATATE Peptide Receptor Radionuclide Therapy: Indigenously Developed Freeze Dried Cold Kit and Biological Response in In-Vitro and In-Vivo Models