Preparation and Clinical Translation Study of 99mTc-labeled Prostate-Specific Membrane Antigen Inhibitor HYNIC-P137

Abstract

To develop a low bladder accumulation SPECT prostate cancer imaging agent, 99mTc-P137 was prepared on the basis of 68Ga-P137 structure, and the probe was subjected to detailed preclinical evaluation and preliminary clinical translation studies. The labeled precursor HYNIC-P137 was prepared by solid-phase synthesis method, and the labeled precursor 99mTc was labeled with EDDA as co-ligand, and the product 99mTc-P137 was quality controlled. The lipid-water partition coefficient and in vitro stability of 99mTc-P137 were examined, and its uptake and inhibition on PSMA-positive and negative cells were investigated. Biodistribution in normal Kunming mice and SPECT/CT imaging in hormonal mice were performed, and finally, clinical translation studies were performed. The results showed that the precursor HYNIC-P137 could be easily obtained from solid-phase synthesis, and the labeled product 99mTc-P137 had a radiochemical purity close to 100%, good in vitro stability and high hydrophilicity. Normal Kunming mouse biodistribution showed rapid blood clearance of this probe, which was mainly metabolized by the kidney. MicroSPECT/CT of tumor-bearing mice showed that 99mTc-P137 was concentrated mainly in PSMA-positive tumors and renal regions, and both could be significantly inhibited, showing a high degree of intra-specific specificity. Clinical translation showed low accumulation of 99mTc-P137 in the bladder, high intrahepatic radioactivity, and good detection performance for prostate cancer foci in situ and lymph node metastases. It was shown that 99mTc-P137 with high affinity and low bladder accumulation is a novel ODAP-based SPECT prostate cancer imaging probe.

Keywords

• prostate-specific membrane antigen
• technetium-99m
• oxalyldiaminopropionic acid