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

TY - JOUR

T1 - (SiFA)SeFe

T2 - A Hydrophilic Silicon-Based Fluoride Acceptor Enabling Versatile Peptidic Radiohybrid Tracers

AU - Deiser, Sandra

AU - Fenzl, Sebastian

AU - König, Victor

AU - Drexler, Marike

AU - Smith, Lydia M

AU - George, Madeleine E

AU - Beck, Roswitha

AU - Witney, Timothy H

AU - Inoue, Shigeyoshi

AU - Casini, Angela

N1 - Publisher Copyright: © 2024 The Authors. Published by American Chemical Society.

PY - 2024/8/8

Y1 - 2024/8/8

N2 - 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 18F for PET imaging or chelation of 177Lu 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.

AB - 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 18F for PET imaging or chelation of 177Lu 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.

UR - http://www.scopus.com/inward/record.url?scp=85200869530&partnerID=8YFLogxK

U2 - 10.1021/acs.jmedchem.4c00924

DO - 10.1021/acs.jmedchem.4c00924

M3 - Article

C2 - 39115131

SN - 0022-2623

VL - 67

SP - 14077

EP - 14094

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 16

M1 - 67

ER -