CLINICAL CANCER RESEARCH | PERSPECTIVES High-Specific-Activity- 131 I-MIBG versus 177 Lu-DOTATATE Targeted Radionuclide Therapy for Metastatic Pheochromocytoma and Paraganglioma Abhishek Jha 1 , David Ta € eb 2 , Jorge A. Carrasquillo 3,4 , Daniel A. Pryma 5 , Mayank Patel 1 , Corina Millo 6 , Wouter W. de Herder 7 , Jaydira Del Rivero 8 , Joakim Crona 9 , Barry L. Shulkin 10 , Irene Virgolini 11 , Alice P. Chen 12 , Bhagwant R. Mittal 13 , Sandip Basu 14 , Joseph S. Dillon 15 , Thomas A. Hope 16 , Carina Mari Aparici 17 , Andrei H. Iagaru 17 , Rodney J. Hicks 18 , Anca M. Avram 19 , Jonathan R. Strosberg 20 , Ali Cahid Civelek 21 , Frank I. Lin 22 , Neeta Pandit-Taskar 3,4 , and Karel Pacak 1 ABSTRACT ◥ Targeted radionuclide therapies (TRT) using 131 I- metaiodobenzylguanidine ( 131 I-MIBG) and peptide receptor radio- nuclide therapy ( 177 Lu or 90 Y) represent several of the therapeutic options in the management of metastatic/inoperable pheochromocy- toma/paraganglioma. Recently, high-specific-activity- 131 I-MIBG ther- apy was approved by the FDA and both 177 Lu-DOTATATE and 131 I- MIBG therapy were recommended by the National Comprehensive Cancer Network guidelines for the treatment of metastatic pheochro- mocytoma/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 pheochromo- cytoma/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. Introduction Targeted radionuclide therapies (TRT) using 131 I- metaiodobenzylguanidine ( 131 I-MIBG) and peptide receptor radio- nuclide therapy (PRRT; 177 Lu or 90 Y) are available for metastatic/ inoperable pheochromocytoma/paraganglioma. It is unclear which therapy is preferable when tumors show uptake by both MIBG [generally 123 I-MIBG single-photon emission CT/CT (SPECT/CT), but potentially also 124 I-MIBG or 18 F-metafluorobenzylguanidine ( 18 F-MFBG) or 18 F-fluorodopamine ( 18 F-FDA) PET/CT] and somato- statin receptor imaging (SSTRI; 111 In-pentetreotide or 68 Ga-DOTA- TATE/TOC/NOC PET/CT or 64 Cu-DOTATATE PET/CT). 131 I-MIBG is a safe and well-tolerated therapy, used since the 1980s with objective, biochemical, and symptomatic responses in patients with paragan- glioma (1). The recent FDA approval of novel high-specific-activity (HSA)- 131 I-MIBG therapy (Azedra Ò ; Progenics Pharmaceuticals, Inc.) in metastatic/inoperable pheochromocytoma/paraganglioma has gen- erated considerable interest (2). Similarly, the recent FDA approval of 1 Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, Maryland. 2 Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Aix- Marseille University, Marseille, France. 3 Department of Radiology, Molecular Imaging and Therapy Service, Memorial Sloan Kettering Cancer Center, New York, New York. 4 Department of Radiology, Weill Cornell Medical College, New York, New York. 5 Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. 6 Department of Positron Emission Tomography, Warren Grant Magnuson Clinical Center, National Insti- tutes of Health, Bethesda, Maryland. 7 Section of Endocrinology, Department of Internal Medicine, ENETS Centre of Excellence, Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, the Netherlands. 8 Developmental Therapeutics Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland. 9 Department of Medical Sciences, Uppsala University, Uppsala, Sweden. 10 Department of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, Tennessee. 11 Department of Nuclear Medicine, Medical University of Innsbruck, Innsbruck, Austria. 12 Division of Cancer Treatment and Diagnosis, NCI, NIH, Bethesda, Maryland. 13 Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India. 14 Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Hospital Annexe, Homi Bhabha National Institute, Mumbai, Maharashtra, India. 15 Department of Internal Med- icine, University of Iowa Hospitals and Clinics, Iowa City, Iowa. 16 Department of Radiology and Biomedical Imaging, University of California, San Francisco, California. 17 Divisions of Nuclear Medicine and Molecular Imaging, Stanford University School of Medicine, Stanford, California. 18 Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia. 19 Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan. 20 Division of Neuroendocrine Tumor/ Department of Gastrointestinal Medicine, Moffitt Cancer Center, Tampa, Florida. 21 Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and Radiological Sciences, Johns Hopkins Medicine, Baltimore, Maryland. 22 Molecular Imaging Program, NCI, NIH, Bethesda, Maryland. N. Pandit-Taskar and K. Pacak contributed equally to this article. Corresponding Authors: Karel Pacak, Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, 10 Center Drive MSC-1109, Bethesda, MD 20892-1109. Phone: 301-402-4594; Fax: 301-402-0884; E-mail: karel@mail.nih.gov; and Neeta Pandit-Taskar, Molecular Imaging &Therapy Svc, Department of Radiology, Member, Memorial Hospital, Memorial Sloan Kettering Cancer Center, New York, NY, Professor, Department of Radiology, Weill Cornell Medical Center, New York, NY, Clinical Director, Center for Targeted Radioimmunotherapy and Theranostics, Ludwig Center for Cancer Immu- notherapy, MSK, Member Researcher, Parker Institute of Cancer Immunotherapy, MSK, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065. Phone: 212-639-3046; Fax: 212-717-3263; E-mail: pandit-n@mskcc.org Clin Cancer Res 2021;27:2989–95 doi: 10.1158/1078-0432.CCR-20-3703 Ó2021 American Association for Cancer Research. AACRJournals.org | 2989 Downloaded from http://aacrjournals.org/clincancerres/article-pdf/27/11/2989/3088289/2989.pdf by guest on 19 December 2023