Feasibility Study of Single-Photon Emission Computed Tomography with Iodine-123 Labeled Metaiodobenzylguanidine for Preclinical Evaluation of Labetalol as a β-Adrenergic Receptor Blocker

Article

作者: Kang, Joo Hyun ; Lee, Eun Sang ; Choi, Yiseul ; Woo, Sang-Keun ; Lee, Kyo Chul ; Chung, Hye Kyung

Among clinically used radiopharmaceuticals, iodine-123 labeled metaiodobenzylguanidine ([¹²³I]mIBG) serves for diagnosing neuroendocrine tumors and obtaining images of myocardial sympathetic innervation. mIBG, a structural analogue of norepinephrine (NE), a neurotransmitter acting in peripheral and central nerves, follows a pathway similar to NE, transmitting signals through the NE transporter (NET) located at synaptic terminals. It moves through the body without decomposing, enabling noninvasive image evaluation. In this study, we aimed to quantify [¹²³I]mIBG uptake in the adrenal glands using small animal single-photon emission computed tomography/computed tomography (SPECT/CT) images post [¹²³I]mIBG administration. We investigated the possibility of assessing the effectiveness of β-adrenergic receptor blockers by quantifying SPECT/CT images and biodistribution results to determine the degree of [¹²³I]mIBG uptake in the adrenal glands treated with labetalol, a known β-adrenergic receptor blocker. Upon intravenous administration of [¹²³I]mIBG to mice, SPECT/CT images were acquired over time to confirm the in vivo distribution pattern, revealing a clear uptake in the adrenal glands. Labetalol inhibited the uptake of [¹²³I]mIBG in cell lines expressing NET. A decrease in [¹²³I]mIBG uptake in the adrenal glands was observed in the labetalol-treated group compared with the normal group through SPECT/CT imaging and biodistribution studies. These results demonstrate that SPECT/CT imaging with [¹²³I]mIBG could be applicable for evaluating the preclinical efficacy of new antihypertensive drug candidates such as labetalol, a β-adrenergic receptor blocker.

2024-05-01·The Cancer Journal

Theranostics in Neuroendocrine Tumors

Review

作者: Mittra, Erik ; Mallak, Nadine ; Pryma, Daniel A. ; O'Brien, Sophia R.

AbstractNeuroendocrine tumors (NETs) are rare tumors that develop from cells of the neuroendocrine system and can originate in multiple organs and tissues such as the bowels, pancreas, adrenal glands, ganglia, thyroid, and lungs. This review will focus on gastroenteropancreatic NETs (more commonly called NETs) characterized by frequent somatostatin receptor (SSTR) overexpression and pheochromocytomas/paragangliomas (PPGLs), which typically overexpress norepinephrine transporter. Advancements in SSTR-targeted imaging and treatment have revolutionized the management of patients with NETs. This comprehensive review delves into the current practice, discussing the use of the various Food and Drug Administration–approved SSTR-agonist positron emission tomography tracers and the predictive imaging biomarkers, and elaborating on 177Lu-DOTATATE peptide receptor radionuclide therapy including the evolving areas of posttherapy imaging practices and peptide receptor radionuclide therapy retreatment. SSTR-targeted imaging and therapy can also be used in patients with PPGL; however, this patient population has demonstrated the best outcomes from norepinephrine transporter-targeted therapy with 131I-metaiodobenzylguanidine. Metaiodobenzylguanidine theranostics for PPGL will be discussed, noting that in 2024 it became commercially unavailable in the United States. Therefore, the use and reported success of SSTR theranostics for PPGL will also be explored.

2023-06-01·Journal of Nuclear Medicine

Efficacy and Safety of¹²⁴I-MIBG Dosimetry-Guided High-Activity¹³¹I-MIBG Therapy of Advanced Pheochromocytoma or Neuroblastoma

Article

作者: Schmitz, Jochen ; Schaarschmidt, Benedikt M ; Unger, Nicole ; Maric, Ines ; Weber, Manuel ; Jentzen, Walter ; Herrmann, Ken ; Bockisch, Andreas ; Poeppel, Thorsten D ; Prochnow, Andre ; Rischpler, Christoph ; Fendler, Wolfgang P

We aim to evaluate the efficacy and safety of ¹²⁴I-metaiodobenzylguanidine (MIBG) dosimetry-guided high-activity ¹³¹I-MIBG therapy of advanced pheochromocytoma or neuroblastoma. Methods: Fourteen patients with advanced pheochromocytoma or neuroblastoma, age 9-69 y, underwent ¹²⁴I-MIBG PET scans and whole-body retention measurements to assess the whole-body dose as a surrogate of bone marrow toxicity and tumor (absorbed) dose per unit of administered activity. Dosimetry results together with individual patient characteristics were combined to guide a single therapeutic activity to achieve a high tumor dose without exceeding toxicity threshold. Toxicity was assessed for hematologic, hepatic, and renal function. Response was evaluated by RECIST, International Society of Pediatric Oncology Europe Neuroblastoma-like score, change in PET uptake, and quantitative PET parameters (SUV_max, SUV_peak, metabolic tumor volume, total lesion glycolysis), as well as visual decrease in number or in visual intensity of lesions on baseline to follow-up ¹²⁴I-MIBG PET/CT. Results: The average therapeutic activity was 14 GBq. Eleven of 14 patients (79%) received each more than 10 GBq. One male patient was treated with a single activity of 50 GBq. Three patients were treated with lower activities between 3.5 and 7.0 GBq. Median overall survival was 85 mo (95% CI), and median progression-free survival was 25 mo (95% CI). Four (29%) and 5 (36%) patients demonstrated response (complete response or partial response) by RECIST and functional imaging, respectively. One patient exceeded whole-body dose of 2 Gy and demonstrated grade 3 hematologic toxicity, which resolved spontaneously within 12 mo after the therapy without the need for further treatment. Three patients (21%) demonstrated transient grade 1 renal toxicity. Conclusion: ¹²⁴I-MIBG dosimetry-guided high-activity ¹³¹I-MIBG therapy in patients with advanced pheochromocytoma or neuroblastoma resulted in durable responses with a low rate of manageable adverse events. Efficacy of ¹²⁴I-MIBG-guided activity escalation should further be assessed in a prospective setting.

100 项与 I-123 metaiodobenzylguanidine 相关的药物交易

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