Several radioligands targeting prostate-specific membrane
antigen (PSMA) have been clinically introduced as a new class of radiotheranostics for the treatment of
prostate cancer. Among them, ((( R)-1-carboxy-2-mcercaptoethyl)carbamoyl)-l-glutamic
acid (MCG) has been successfully labeled with
radioisotopes for
prostate cancer imaging. The aim of this study is to conjugate MCG with an
albumin binding moiety to further improve the in vivo pharmacokinetics. MCG was conjugated with an
Evans blue (EB) derivative for
albumin binding and a
DOTA 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 the biodistribution and
tumor uptake of 86Y-DOTA-EB-MCG.
DOTA-EB-MCG was also labeled with 90Y for
radionuclide therapy. Besides
tumor growth measurement,
tumor response to escalating therapeutic doses were also evaluated by immunohistochemistry and fluorescence microscopy. Based on quantification from 86Y-DOTA-EB-MCG PET images, the tracer uptake in PC3-PIP
tumors increased from 22.33 ± 2.39%ID/g at 1 h post-injection (p.i.), to the peak of 40.40 ± 4.79%ID/g at 24 h p.i. Administration of 7.4 MBq of 90Y-DOTA-EB-MCG resulted in significant regression of
tumor growth in PSMA positive xenografts. No apparent toxicity or
body weight loss was observed in all treated mice. Modification of MCG with an
Evans blue 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.