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Overview of Results of Peptide Receptor Radionuclide Therapy with 3 Radiolabeled Somatostatin Analogs

¹ Department of Nuclear Medicine, Erasmus Medical Center, University Hospital Rotterdam, Rotterdam, The Netherlands
² Department of Nuclear Medicine, University Hospital Basel, Basel, Switzerland
³ Department of Nuclear Medicine, European Institute of Oncology, Milan, Italy
⁴ Division of Hematology and Oncology, Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana
⁵ Department of Nuclear Medicine, Universitaire Catholique Louvain, Brussels, Belgium
⁶ Lee Moffitt Cancer Center, University of South Florida, Tampa, Florida
⁷ Division of Endocrinology, Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa

A new treatment modality for inoperable or metastasized gastroenteropancreatic tumors is the use of radiolabeled somatostatin analogs. Initial studies with high doses of [¹¹¹In-diethylenetriaminepentaacetic acid (DTPA)⁰]octreotide in patients with metastasized neuroendocrine tumors were encouraging, although partial remissions were uncommon. Another radiolabeled somatostatin analog that is used for peptide receptor radionuclide therapy (PRRT) is [⁹⁰Y-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)⁰,Tyr³]octreotide. Various phase 1 and phase 2 PRRT trials have been performed with this compound. Despite differences in the protocols used, complete and partial remissions in most of the studies with [⁹⁰Y-DOTA⁰,Tyr³]octreotide were in the same ranges, 10%–30%; these ranges were higher than those obtained with [¹¹¹In-DTPA⁰]octreotide. Treatment with the newest radiolabeled somatostatin analog, [¹⁷⁷Lu-DOTA⁰,Tyr³]octreotate, which has a higher affinity for the subtype 2 somatostatin receptor, resulted in complete or partial remissions in 30% of 76 patients. Tumor regression was positively correlated with a high level of uptake on OctreoScan imaging, a limited hepatic tumor mass, and a high Karnofsky performance score. Treatment with radiolabeled somatostatin analogs is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumors. Symptomatic improvement may occur with all ¹¹¹In-, ⁹⁰Y-, or ¹⁷⁷Lu-labeled somatostatin analogs that have been used for PRRT. The results obtained with [⁹⁰Y-DOTA⁰,Tyr³]octreotide and [¹⁷⁷Lu-DOTA⁰,Tyr³]octreotate are very encouraging in terms of tumor regression. Also, if kidney protective agents are used, the side effects of this therapy are few and mild, and the duration of the therapy response for both radiopharmaceuticals is more than 2 y. These data compare favorably with those for the limited number of alternative treatment approaches.

Key Words: somatostatin • somatostatin receptor • radionuclide therapy • gastroenteropancreatic tumors

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