Development and clinical potential of 18F-PSiMA for prostate cancer PET imaging
Prostate-specific membrane antigen (PSMA) is a key target for diagnosing prostate cancer through positron emission tomography (PET). While 68Ga-labeled PSMA compounds are widely used, 18F-labeled PSMA inhibitors have gained traction for clinical tumor imaging. We previously investigated PSMA-targeti...
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| Hauptverfasser: | , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
09 May 2025
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| In: |
RSC medicinal chemistry
Year: 2025, Jahrgang: 16, Heft: 8, Pages: 3633-3644 |
| ISSN: | 2632-8682 |
| DOI: | 10.1039/D5MD00275C |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1039/D5MD00275C Verlag, kostenfrei, Volltext: https://pubs.rsc.org/en/content/articlelanding/2025/md/d5md00275c 
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| Verfasserangaben: | Lexi Gower-Fry, Justin J. Bailey, Melinda Wuest, Susan Pike, Alexey Kostikov, Andreas Dorian, Carmen Wängler, Frank Wuest and Ralf Schirrmacher |
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| 520 | |a Prostate-specific membrane antigen (PSMA) is a key target for diagnosing prostate cancer through positron emission tomography (PET). While 68Ga-labeled PSMA compounds are widely used, 18F-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 in vivo biodistribution. This led to the development of 18F-PSiMA, a SiFA-based radiotracer with an optimized linker exhibiting favorable PSMA potency (IC50 = 154 ± 47 nM in LNCaP cells). 18F-PSiMA radiosynthesis with low to high concentrations of 18F and precursor achieved molar activities (Am) of 10.9-82.5 GBq μmol−1 and showed a 24-38% increase in tumor uptake in LNCaP tumors (SUV60min 1.56 ± 0.18; 7.23 ± 0.75% ID per g at lower Am and SUV60min 1.90 ± 0.29; 9.62 ± 1.29% ID per g at higher Am) compared to our previous lead, 18F-SiFA-Asp2-PEG3-PSMA. PSMA specificity was confirmed by a 20 ± 10% reduction in SUV60min upon co-injection with DCFPyl. These promising in vitro and in vivo results support further clinical translation of 18F-PSiMA for prostate cancer PET imaging. | ||
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