Gower-Fry Lexi, Bailey Justin J, Wuest Melinda, Pike Susan, Kostikov Alexey, Dorian Andreas, Wängler Carmen, Wuest Frank, Schirrmacher Ralf
Department of Chemistry, University of Alberta Edmonton Alberta Canada
Department of Oncology, University of Alberta Edmonton Alberta Canada.
RSC Med Chem. 2025 May 9. doi: 10.1039/d5md00275c.
Prostate-specific membrane antigen (PSMA) is a key target for diagnosing prostate cancer through positron emission tomography (PET). While Ga-labeled PSMA compounds are widely used, F-labeled PSMA inhibitors have gained traction for clinical tumor imaging. We previously investigated PSMA-targeting compounds based on the Lys-urea-Glu motif, incorporating a silicon fluoride-acceptor (SiFA) and chemical auxiliaries to enhance biodistribution. This led to the development of F-PSiMA, a SiFA-based radiotracer with an optimized linker exhibiting favorable PSMA potency (IC = 154 ± 47 nM in LNCaP cells). F-PSiMA radiosynthesis with low to high concentrations of F and precursor achieved molar activities ( ) of 10.9-82.5 GBq μmol and showed a 24-38% increase in tumor uptake in LNCaP tumors (SUV 1.56 ± 0.18; 7.23 ± 0.75% ID per g at lower and SUV 1.90 ± 0.29; 9.62 ± 1.29% ID per g at higher ) compared to our previous lead, F-SiFA-Asp-PEG-PSMA. PSMA specificity was confirmed by a 20 ± 10% reduction in SUV upon co-injection with DCFPyl. These promising and results support further clinical translation of F-PSiMA for prostate cancer PET imaging.
前列腺特异性膜抗原（PSMA）是通过正电子发射断层扫描（PET）诊断前列腺癌的关键靶点。虽然镓标记的PSMA化合物被广泛使用，但氟标记的PSMA抑制剂在临床肿瘤成像中越来越受到关注。我们之前研究了基于Lys-尿素-Glu基序的PSMA靶向化合物，引入了氟化硅受体（SiFA）和化学助剂以增强生物分布。这导致了F-PSiMA的开发，这是一种基于SiFA的放射性示踪剂，其连接子经过优化，表现出良好的PSMA亲和力（在LNCaP细胞中的IC = 154 ± 47 nM）。使用低至高浓度的氟和前体进行F-PSiMA的放射性合成，获得的摩尔活度（ ）为10.9-82.5 GBq/μmol，并且与我们之前的先导化合物F-SiFA-Asp-PEG-PSMA相比，LNCaP肿瘤的肿瘤摄取增加了24-38%（较低 时SUV为1.56 ± 0.18；每克7.23 ± 0.75% ID，较高 时SUV为1.90 ± 0.29；每克9.62 ± 1.29% ID）。与DCFPyl共同注射后SUV降低20 ± 10%证实了PSMA的特异性。这些有前景的 和 结果支持F-PSiMA在前列腺癌PET成像方面进一步向临床转化。
