Radiolabeled somatostatin analogs for cancer treatment. Review

Currently, a specific action on tumor cells with minimal toxicity to healthy tissues is the main requirement for radionuclide therapy of cancer. The molecular target of selective antitumor therapy is determined by somatostatin receptors (SSTR) overexpression in various tumors and its metastases. Natural somatostatin cannot be used as a vector molecule for radionuclide delivery due to its short half-life in blood (1-3 min). Synthetic peptide somatostatin analogs labeled with therapeutic radionuclides (radiopeptides) also have high affinity to SSTR and better pharmacokinetics compared to somatostatin and therefore they are of great interest for targeted cancer therapy, also called peptide-receptor radionuclide therapy (PRRT). The data about the most important to date somatostatin analogs labeled with 111In, 90Y, 177Lu radionuclides for therapy of tumors overexpressing SSTR is presented. The results of treatment efficacy and toxicity profile of PRRT, which is administered with various generations of targeting SSTR radiopharmaceuticals, including the randomized controlled trial NETTER-1, is reviewed. In addition, some strategies for optimization of PRRT such as tandem therapy, intra-arterial administration of radiopharmaceuticals, their modification for better pharmacokinetic properties, and the development of new compounds containing a-emitting radionuclides or SSTR antagonist analogs are discussed.