High-Specific-Activity-131I-MIBG versus 177Lu-DOTATATE Targeted Radionuclide Therapy for Metastatic Pheochromocytoma and Paraganglioma

Abstract

Targeted radionuclide therapies (TRT) using ¹³¹I-metaiodobenzylguanidine (¹³¹I-MIBG) and peptide receptor radionuclide therapy (¹⁷⁷Lu or ⁹⁰Y) represent several of the therapeutic options in the management of metastatic/inoperable pheochromocytoma/paraganglioma. Recently, high-specific-activity-¹³¹I-MIBG therapy was approved by the FDA and both ¹⁷⁷Lu-DOTATATE and ¹³¹I-MIBG therapy were recommended by the National Comprehensive Cancer Network guidelines for the treatment of metastatic pheochromocytoma/paraganglioma. However, a clinical dilemma often arises in the selection of TRT, especially when a patient can be treated with either type of therapy based on eligibility by MIBG and somatostatin receptor imaging. To address this problem, we assembled a group of international experts, including oncologists, endocrinologists, and nuclear medicine physicians, with substantial experience in treating neuroendocrine tumors with TRTs to develop consensus and provide expert recommendations and perspectives on how to select between these two therapeutic options for metastatic/inoperable pheochromocytoma/paraganglioma. This article aims to summarize the survival outcomes of the available TRTs; discuss personalized treatment strategies based on functional imaging scans; address practical issues, including regulatory approvals; and compare toxicities and risk factors across treatments. Furthermore, it discusses the emerging TRTs.

Figure 1.. Selection of HSA-¹³¹I-MIBG over PRRT for metastatic PPGL based on superior norepinephrine transporter expression imaged by ¹²⁴I-MIBG PET/CT and compared with ¹⁸F-fluorodeoxyglucose PET/CT

The anterior maximum intensity projection images of (A) ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography-computed tomography (PET/CT), (B) somatostatin receptor imaging by ⁶⁸Ga-DOTA(0)-Tyr(3)-octreotate (⁶⁸Ga-DOTATATE) PET/CT, and (C) norepinephrine transporter imaging by ¹²⁴I-metaiodobenzylguanidine (¹²⁴I-MIBG) PET/CT in a case of widely metastatic PPGL. ¹²⁴I-MIBG demonstrates more disease sites than ¹⁸F-FDG as well as having significantly more intense and numerous lesion uptake than ⁶⁸Ga-DOTATATE, making MIBG therapy the preferred option for treatment in this case. Advantages of comparing PET to PET and ability to do prospective dosimetry are potential advantages of ¹²⁴I-MIBG over ¹²³I-MIBG although this technique is not widely available.

Figure 2.. Selection of HSA-¹³¹I-MIBG vs PRRT for metastatic pheochromocytoma/paraganglioma based on expression of somatostatin receptor and norepinephrine transporter

Panel (A) demonstrates superior detection of tumors by norepinephrine transporter imaging by ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG, anterior and posterior planar images on the right) compared to somatostatin receptor imaging by ⁶⁸Ga-DOTA(0)-Tyr(3)-octreotate (⁶⁸Ga-DOTATATE) positron emission tomography-computed tomography (PET/CT) [maximum intensity projection (MIP) image on the left] in a 64-year-old man revealing a recurrent tumor in the left adrenalectomy bed along with retroperitoneal lesions, left supraclavicular lymph node and multiple scattered bony metastatic disease including cervical bone metastasis. Panel (B) demonstrates the superior detection of tumors by ⁶⁸Ga-DOTATATE PET/CT (MIP image on the left) compared to ¹²³I-MIBG (anterior and posterior planar images on the right) in a 33-year-old woman revealing an extensive recurrent tumor in the right adrenalectomy bed at the level of right mid kidney along with metastatic disease in both lungs, scattered bone metastases in vertebral bodies, axial, and proximal appendicular skeleton. The planar images of ¹²³I-MIBG only reveals mild uptake of recurrent tumor in the right adrenalectomy bed. Panel (C) demonstrates the similar pattern of tumor detection by both ⁶⁸Ga-DOTATATE PET/CT (MIP image on the left) and ¹²³I-MIBG (anterior and posterior planar images on the right) in a 27-year-old female patient revealing metastatic liver lesions and multiple scattered bony metastatic disease. While interpreting the scans, it is critical to account for the inherent differences between single photon emission imaging (¹²³I-MIBG scintigraphy) and PET (⁶⁸Ga-DOTATATE) imaging as contrast recovery, sensitivity, and spatial resolution are far superior for PET imaging. Therefore, some of the smaller lesions seen on ⁶⁸Ga-DOTATATE MIP may not be visible on planar images of ¹²³I-MIBG scintigraphy despite adequate MIBG uptake. This should not be confused for greater uptake or a higher likelihood of response to therapy. ¹²⁴I-MIBG and ¹⁸F-MFBG for PET that are under development should help simplify the comparison between MIBG and SSTRI scans in a given patient.