Optimization of ODAP-Urea-based dual-modality PSMA targeting probes for sequential PET-CT and optical imaging.

Abstract

Prostate-specific membrane antigen (PSMA) is emerging as a promising target to specifically image prostate cancer. Dual-modality probe combining radionuclide imaging and near-infrared fluorescence navigation targeting PSMA would enable both the preoperative staging and intraoperative detection of the tumor lesions. To overcome one of the key barriers for achieving high contrast imaging at both early and late time points, we optimized the pharmacokinetics of dual-modality probes based on oxalyldiaminopropionic acid-urea (ODAP-Urea) PSMA inhibitors recently developed. Four dual-modality probes with variable hydrophilicity were synthesized and evaluated. They displayed good optical properties (λem max = 835 nm, QY = 0.67%-1.50%), high affinity to PSMA (Ki = 2.09 ± 1.71-4.15 ± 2.20 nM) and PSMA specific cellular uptake (0.48 ± 0.01% - 0.64 ± 0.04% IA/105 LNCaP cells) upon labeled with 68Ga. In vivo studies showed that [68Ga]Ga-P3 exhibited an optimum pharmacokinetic property with high specific tumor uptake (SUVmax = 1.88 ± 0.36, at 1 h) in medium level PSMA expressing 22Rv1 tumor model and high tumor-to-muscle ratio (12.56 ± 2.63, at 1 h). Specific fluorescence imaging could also be achieved with high contrast for later time points (tumor-to-background ratio = 11.63 ± 4.16 at 24 h). This study demonstrates that ODAP-Urea-based P3 has the potential for PET imaging and intraoperative optical imaging of prostate cancer.

• Authors: Yuan Li, Xiaojiang Duan, Hongchuang Xu, Jingming Zhang, Haoxi Zhou, Xiaojun Zhang, Jinming Zhang, Zhi Yang, Zhenhua Hu, Ning Zhang, Jie Tian, Xing Yang
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 66 Pg. 116810 (07 15 2022) ISSN: 1464-3391 [Electronic] England
• PMID: 35580538 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier Ltd. All rights reserved.

Chemical References

• Amino Acids, Diamino
• Gallium Radioisotopes
• oxalyldiaminopropionic acid
• Urea
• Glutamate Carboxypeptidase II

Topics

• Amino Acids, Diamino
• Cell Line, Tumor
• Gallium Radioisotopes
• Glutamate Carboxypeptidase II (metabolism)
• Humans
• Male
• Optical Imaging (methods)
• Positron Emission Tomography Computed Tomography (methods)
• Prostatic Neoplasms (diagnostic imaging, pathology)
• Tissue Distribution
• Urea