Abstract
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Introduction: Several radioligands targeting prostate-specific membrane antigen (PSMA) have been clinically introduced as a new class of radiotheranostics for imaging and treating prostate cancer. Among them, methyl cysteine-glutamate urea (MCG) has been successfully labeled with both fluorescent dyes and radioisotopes for prostate cancer imaging. The aim of this study was to conjugate MCG with an albumin binding moiety to further improve tumor delivery and increase therapeutic index. Materials and Methods: MCG was conjugated with an Evans blue (EB) derivative for albumin binding and a DOTA molecule as a metal chelator. PSMA positive PC3-PIP and PSMA negative PC3 cells were used for both in vitro and in vivo studies. Longitudinal PET imaging was performed at 1, 4, 24, and 48 h post injection to evaluate biodistribution and tumor uptake of 86Y-DOTA-EB-MCG. DOTA-EB-MCG was also labeled with 90Y for radioligand therapy (RLT). Results: Based on region of analysis (ROI) of 86Y-DOTA-EB-MCG PET images, the tracer uptake in PSMA+ PC-3 PIP tumors increased from 18.74 ± 1.28 %ID/g at 1 h p.i. to the peak of 39.47 ± 3.04 %ID/g at 24 h p.i., and was still as high as 34.05 ± 4.06 % ID/g at 48 h p.i.. Administration of 3.7 MBq of 90Y-DOTA-EB-MCG resulted in significant PC3-PIP tumor growth inhibition. When a 7.4 MBq of 90Y-DOTA-EB-MCG single dose was used, the tumors were completely eradicated. As a comparison, 7.4 MBq of 90Y-DOTA-MCG only showed marginal delay of tumor growth. Conclusion: Modification of MCG with the EB derivative resulted in a highly efficient prostate cancer targeting agent (EB-MCG), which showed great potential in prostate cancer treatment after being labeled with therapeutic radioisotopes.
