(SiFA)SeFe:\nA Hydrophilic Silicon-Based Fluoride Acceptor\nEnabling Versatile Peptidic Radiohybrid Tracers

The radiohybrid (rh) concept to design targeted (and\nchemically\nidentical) radiotracers for imaging or radionuclide therapy of tumors\nhas gained momentum. For this strategy, a new bifunctional Silicon-based\nFluoride Acceptor (SiFA) moiety <b>(SiFA)SeFe</b> was synthesized,\nendowed with improved hydrophilicity and high versatility of integration\ninto rh-compounds. Preliminary radiolabeling and stability studies\nunder different conditions were conducted using model bioconjugate\npeptides. Further, three somatostatin receptor 2 (sstR2)-targeted\nrh-compounds (<b>(SiFA)SeFe-rhTATE1–3</b>, TATE = (Tyr<sup>3</sup>)-octreotate) were developed. Compound <b>(SiFA)SeFe-rhTATE3</b>, enables labeling with <sup>18</sup>F for PET imaging or chelation\nof <sup>177</sup>Lu for therapy. The rh-compounds possess comparable\nreceptor binding affinity and <i>in vitro</i> performance\nas good as the clinically proven gold standards. SstR2-specificity\nwas further shown for <b>(SiFA)SeFe-rhTATE2</b> using the chicken\nchorioallantoic membrane (CAM) model. The biodistribution of two compounds\nin mice showed high accumulation in tumors and excretion via the kidneys,\ndemonstrating the clinical applicability of the <b>(SiFA)SeFe</b> moiety.