Radiolabeled somatostatin receptor (sstr) antagonists have shown superiority in different preclinical and clinical settings compared with the well-established and clinically used agonists for targeting sstr-expressing tumors, with regard to pharmacokinetics, tumor uptake, and retention. The theranostic pair 177 Lu-OPS201/68 Ga-OPS202, based on the sstr2 antagonist JR11 (Cpa-c[d-Cys-Aph(Hor)-d-Aph(Cbm)-Lys-Thr-Cys]-d-Tyr-NH2 ), is the most advanced pair of the antagonist family in terms of preclinical development and is currently under clinical evaluation. OPS201 and OPS202 share the same amino acid sequence (JR11) but feature different conjugated chelators needed for radiolabeling, DOTA for OPS201 and NODAGA for OPS202. In this review, the design and development of the peptidic analog, JR11, and the selection of chelators and radiometals that led to 177 Lu-OPS201/68 Ga-OPS202 are discussed. Furthermore, the preclinical evaluation of both radiolabeled analogs from bench to bedside and the clinical trials involving the theranostic pair are presented.
Keywords: antagonist; neuroendocrine tumors; peptide receptor radionuclide therapy; positron emission tomography (PET); somatostatin receptors; theranostics.
© 2019 John Wiley & Sons, Ltd.