Radiolabeled somatostatin analogs for cancer treatment. Review

Currently, a specific action on tumor cells with minimal toxicity to healthy tissues is the main re-quirement for radionuclide therapy of cancer. The molecular target of selective antitumor therapy is determined by somatostatin receptors (SSTR) overexpression in various tumors and its metas-tases. 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 thera-peutic 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, al-so called peptide-receptor radionuclide therapy (PRRT). The data about the most important to date somatostatin analogs labeled with In-111, Y-90, Lu-177 radionuclides for therapy of tumors over-expressing SSTR is presented. The results of treatment efficacy and toxicity profile of PRRT, which is administered with various generations of targeting SSTR radiopharmaceuticals, includ-ing the randomized controlled trial NETTER-1, is reviewed. In addition, some strategies for opti-mization of PRRT such as tandem therapy, intra-arterial administration of radiopharmaceuticals, their modification for better pharmacokinetic properties, and the development of new compounds containing alfa-emitting radionuclides or SSTR antagonist analogs are discussed.