A sstR2-targeted radiohybrid theranostic agent for PET imaging and β^- therapy with excellent preclinical performance

The radiohybrid (rh) design of radiopharmaceuticals has recently produced new theranostics suitable for both positron emission tomography (PET) imaging and peptide receptor radionuclide therapy (PRRT). This approach aims to address the limitations of current medical radionuclides by offering a new strategy for combining radionuclides that previously lacked both therapeutic and diagnostic applications. Here, we report on a somatostatin receptor subtype 2 (sstR2)-targeted radiohybrid compound, rhTATE4, which features a bifunctional silicon-based fluoride acceptor (SiFA) - named (SiFA)SeFe - for ¹⁸F-labeling, along with a DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) chelator for ¹⁷⁷Lu-coordination. The rh-theranostic agent demonstrates similar in vitro behavior compared to the gold standards [¹⁷⁷Lu]Lu-DOTA-TATE and SiFAlin-TATE, along with an exceptionally high tumor uptake (53.58 ± 5.51% ID/g for the radiofluorinated version) after 1 h post-injection in AR42J tumor-bearing mice, making it ideal for imaging. Moreover, clearance from normal tissues and considerable tumor retention (10.32 ± 7.04%ID/g) for [¹⁷⁷Lu]Lu-TATE4 were observed at 24 p.i., suggesting good therapeutic applicability.