Long-Term Outcome and Toxicity After Dose-Intensified Treatment with <sup>131</sup>I-MIBG for Advanced Metastatic Carcinoid Tumors

Ezziddin, Samer; Sabet, Amir; Logvinski, Timur; Alkawaldeh, Khaled; Yong-Hing, Charlotte J.; Ahmadzadehfar, Hojjat; Grünwald, Frank; Biersack, Hans‐Jürgen

doi:10.2967/jnumed.112.119313

Cited by 28 publications

(20 citation statements)

References 38 publications

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“…Both studies and case reports have reported the successful use in patients with carcinoid syndrome of the control of the symptoms of the hormone-excess state by using: everolimus[•38]; PRRT[•56, 57, 66, 95, •96, •148]; liver-directed therapies including TACE/TAE[70, 72, •73, 77, 95, 98, 149]; radioembolization[70, 150, 151]; RFA[80, 81, 83, 95, 152]; by increasing the dosage of octreotide/Lanreotide in refractory cases[94, 97, 153–155]; use of cytoreductive surgery[23, 95, 156–160]; use of 131 I-MIBG[95, 105, 106, 108, 110, •161, 162–164]; with the use of the tryptophan hydroxylase inhibitor, Telotristat[108, 113, 114, ••116, •117, 118, 119] and with pasireotide in octreotide resistant cases[•122]. …”

Section: Summary Of Recent Advances In Management Of Specific Hormmentioning

confidence: 99%

Treatment of symptomatic neuroendocrine tumor syndromes: recent advances and controversies

Ito¹,

Lee²,

Jensen³

2016

Expert Opinion on Pharmacotherapy

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Introduction Neuroendocrine tumors(NETs), once thought rare, are increasing in frequency in most countries and receiving increasing-attention. NETs present two-treatment problems. A proportion is functional, hormone-excess-state(F-NET), each of which must be treated. Recently, there are many advances, well-covered in reviews/consensus papers on imaging-NETs;new, novel anti-tumor treatments and understanding their pathogenesis. However, little attention has been paid to advances in the treatment of the hormone-excess-state. These advances are usually reported in case-series, and case-reports with few large studies. In this paper these advances are reviewed. Areas covered Advances in the last 5-years are concentrated on, but a review up to 10-years was performed. PubMed and other databases(Cochrane, etc) were searched for F-NET-syndromes including carcinoid-syndrome, as well as meeting-abstracts on NETs. All advances that controlled hormone-excess-states or facilitated-control were covered. These include new medical-therapies[serotonin-synthesis inhibitors(telotristat), Pasireotide, new agents for treating ACTHomas], increased dosing with conventional therapies(octreotide-LAR, Lanreotide-Autogel), mTor inhibitors(everolimus), Tyrosine-kinase inhibitors(sunitinib), cytoreductive surgery, liver-directed therapies(embolization, chemoembolization, radioembolization, RFA), peptide radio-receptor-therapy(PRRT) and 131I-MIBG, ablation of primary F-NETs. Expert Opinion Although many of the newer therapies controlling the hormone-excess-states in F-NETs are reported in relatively few patients, all the approaches show promise. Their description also generates some controversies/unresolved areas, such as the order of these new treatments, their longterm-efficacy, and effectiveness of combinations which may require large, controlled studies.

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Section: Summary Of Recent Advances In Management Of Specific Hormmentioning

confidence: 99%

Treatment of symptomatic neuroendocrine tumor syndromes: recent advances and controversies

Ito¹,

Lee²,

Jensen³

2016

Expert Opinion on Pharmacotherapy

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“…It shows energy dependent uptake mediated by nor-epinephrine transporter in cells rich in sympathetic neurons. It is used both as a diagnostic and therapeutic tool in neuroendocrine tumors and neuroblastoma [46][47][48].…”

Section: Labelled Mibgmentioning

confidence: 99%

The role of iodine-124 positron emission tomography in molecular imaging

Mahajan

Divgi

2016

Clin Transl Imaging

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Radioactive iodine has been, in various forms, the mainstay of Nuclear Medicine. Iodine-123 is the most widely used iodine isotope for single photon imaging. Iodine-125 continues to be used in diverse applications from in vitro radioassay to in vivo estimation of various pathophysiologic correlates. Iodine-131 ( 131 I), useful for imaging as well as therapy, has contributed more than any other radionuclide to the growth and sustenance of Nuclear Medicine. Positron emission tomography (PET) is an indispensable tool in current clinical practice, spurred by the rapid and increasing availability of radiopharmaceuticals for in vivo imaging. Most clinical PET imaging utilizes fluorine-18; there is a need for positron emitters with longer half-lives, suitable for imaging larger molecules of interest. Iodine-124 ( 124 I) has approximately 23 % positron emission; its 4-day half-life lends itself to sequential imaging, and its dosimetry is comparable to iodine-131. Iodine can be easily attached to a variety of molecules without alteration of physico-chemical or biologic properties. PET with 124 I-labeled molecules enables longitudinal in vivo assessment of their distribution; such pharmacokinetic and biodistribution information has considerable utility in oncologic and non-oncologic applications. We will provide a clinical perspective on the physical and chemical characteristics of 124 I, as the iodide, as well as radiolabeled to a wide variety of molecules of interest.Radioiodination is accomplished based on the chemical and biologic nature of the ligand to be studied, and issues of relevance will be highlighted. We will conclude by describing the current and potential future clinical applications of 124 I-based tracers used for molecular imaging in diagnosis and therapy.

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“…Because of their origin, several neuroendocrine tumors express the NET on their cell membranes. These tumors include gastroenteropancreatic neuroendocrine tumors, medullary thyroid carcinomas, and PPGs [38,39,40]. Approximately 50–60% of PPGs express the NET in their cell membranes [41,42].…”

Section: The Norepinephrine Transportermentioning

confidence: 99%

Targeted Radionuclide Therapy for Patients with Metastatic Pheochromocytoma and Paraganglioma: From Low-Specific-Activity to High-Specific-Activity Iodine-131 Metaiodobenzylguanidine

Jiménez

Erwin

Chasen

2019

Cancers

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Low-specific-activity iodine-131–radiolabeled metaiodobenzylguanidine (I-131-MIBG) was introduced last century as a potential systemic therapy for patients with malignant pheochromocytomas and paragangliomas. Collective information derived from mainly retrospective studies has suggested that 30–40% of patients with these tumors benefit from this treatment. A low index of radioactivity, lack of therapeutic standardization, and toxicity associated with intermediate to high activities (absorbed radiation doses) has prevented the implementation of I-131-MIBG’s in clinical practice. High-specific-activity, carrier-free I-131-MIBG has been developed over the past two decades as a novel therapy for patients with metastatic pheochromocytomas and paragangliomas that express the norepinephrine transporter. This drug allows for a high level of radioactivity, and as yet is not associated with cardiovascular toxicity. In a pivotal phase two clinical trial, more than 90% of patients achieved partial responses and disease stabilization with the improvement of hypertension. Furthermore, many patients exhibited long-term persistent antineoplastic effects. Currently, the high-specific-activity I-131-MIBG is the only approved therapy in the US for patients with metastatic pheochromocytomas and paragangliomas. This review will discuss the historical development of high-specific-activity I-131-MIBG, its benefits and adverse events, and future directions for clinical practice applicability and trial development.

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Long-Term Outcome and Toxicity After Dose-Intensified Treatment with ¹³¹I-MIBG for Advanced Metastatic Carcinoid Tumors

Cited by 28 publications

References 38 publications

Treatment of symptomatic neuroendocrine tumor syndromes: recent advances and controversies

Treatment of symptomatic neuroendocrine tumor syndromes: recent advances and controversies

The role of iodine-124 positron emission tomography in molecular imaging

Targeted Radionuclide Therapy for Patients with Metastatic Pheochromocytoma and Paraganglioma: From Low-Specific-Activity to High-Specific-Activity Iodine-131 Metaiodobenzylguanidine

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Long-Term Outcome and Toxicity After Dose-Intensified Treatment with 131I-MIBG for Advanced Metastatic Carcinoid Tumors

Cited by 28 publications

References 38 publications

Treatment of symptomatic neuroendocrine tumor syndromes: recent advances and controversies

Treatment of symptomatic neuroendocrine tumor syndromes: recent advances and controversies

The role of iodine-124 positron emission tomography in molecular imaging

Targeted Radionuclide Therapy for Patients with Metastatic Pheochromocytoma and Paraganglioma: From Low-Specific-Activity to High-Specific-Activity Iodine-131 Metaiodobenzylguanidine

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Product

Resources

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Long-Term Outcome and Toxicity After Dose-Intensified Treatment with ¹³¹I-MIBG for Advanced Metastatic Carcinoid Tumors