Radiolabeled Somatostatin Analogs-A Continuously Evolving Class of Radiopharmaceuticals

Somatostatin receptors (SSTs) are recognized as favorable molecular targets in neuroendocrine tumors (NETs) and neuroendocrine neoplasms (NENs), with subtype 2 (SST₂) being the predominantly and most frequently expressed. PET/CT imaging with ⁶⁸Ga-labeled SST agonists, e.g., ⁶⁸Ga-DOTA-TOC (SomaKit TOC^®) or ⁶⁸Ga-DOTA-TATE (NETSPOT^®), plays an important role in staging and restaging these tumors and can identify patients who qualify and would potentially benefit from peptide receptor radionuclide therapy (PRRT) with the therapeutic counterparts ¹⁷⁷Lu-DOTA-TOC or ¹⁷⁷Lu-DOTA-TATE (Lutathera^®). This is an important feature of SST targeting, as it allows a personalized treatment approach (theranostic approach). Today, new developments hold promise for enhancing diagnostic accuracy and therapeutic efficacy. Among them, the use of SST₂ antagonists, such as JR11 and LM3, has shown certain advantages in improving image sensitivity and tumor radiation dose, and there is evidence that they may find application in other oncological indications beyond NETs and NENs. In addition, PRRT performed with more cytotoxic α-emitters, such as ²²⁵Ac, or β^- and Auger electrons, such as ¹⁶¹Tb, presents higher efficacy. It remains to be seen if any of these new developments will overpower the established radiolabeled SST analogs and PRRT with β^--emitters.