Somatostatin Analogues and Radionuclides Used in Therapy

Peptide receptor radionuclide therapy (PRRT) is a very promising new treatment modality for inoperable or metastasized gastroenteropancreatic neuroendocrine tumors (GEPNETs). Various combinations of somatostatin analogues, chelators, and radionuclides can be used for PRRT and have been tested in vitro and in vivo. The affinity for the five different somatostatin receptors is considerably affected by small structural modifications in the radioligand molecule, chelator substitution, and/or metal replacement, as well as by the different charges of different radiolabeled analogues and by the degree of hydrophilicity of these compounds. Internalization of the somatostatin-radionuclide ligand after binding to the tumor cell seems to play a pivotal role for the success of tumor targeting by PRRT, especially when using radiometals with a short tissue penetration range. New peptides under investigation for their use in tumor imaging or PRRT, as the so-called pansomatostatins and somatostatin antagonists, mostly lack this ability of internalization. Radiolabeled peptides used in PRRT are [111In-DTPA0]octreotide (111In-octreotide), [90Y-DOTA0,Tyr3]octreotide (90Y-DOTATOC), and [177Lu-DOTA0,Tyr3]octreotate (177Lu-DOTATATE). 90Y-DOTATOC and 177Lu-DOTATATE are superior when compared to 111In-octreotide in terms of tumor size reduction.