(SiFA)SeFe: A Hydrophilic Silicon-Based Fluoride Acceptor Enabling Versatile Peptidic Radiohybrid Tracers

Abstract

High Resolution Image Download MS PowerPoint Slide The radiohybrid (rh) concept to design targeted (and chemically identical) radiotracers for imaging or radionuclide therapy of tumors has gained momentum. For this strategy, a new bifunctional Silicon-based Fluoride Acceptor (SiFA) moiety (SiFA)SeFe was synthesized, endowed with improved hydrophilicity and high versatility of integration into rh-compounds. Preliminary radiolabeling and stability studies under different conditions were conducted using model bioconjugate peptides. Further, three somatostatin receptor 2 (sstR2)-targeted rh-compounds ( (SiFA)SeFe-rhTATE1–3, TATE = (Tyr 3 )-octreotate) were developed. Compound (SiFA)SeFe-rhTATE3, enables labeling with 18 F for PET imaging or chelation of 177 Lu for therapy. The rh-compounds possess comparable receptor binding affinity and in vitro performance as good as the clinically proven gold standards. SstR2-specificity was further shown for (SiFA)SeFe-rhTATE2 using the chicken chorioallantoic membrane (CAM) model. The biodistribution of two compounds in mice showed high accumulation in tumors and excretion via the kidneys, demonstrating the clinical applicability of the (SiFA)SeFe moiety.