Author/Authors :
Wang, Yuebing Department of Biochemistry - School of Medicine - Nankai University - Tianjin, China , Shao, Guoqiang Department of Nuclear Medicine - Nanjing First Hospital, Nanjing Medical University - Nanjing, China , Wu, Jianping Department of Urology Surgery - Nanjing First Hospital - Nanjing Medical University - Nanjing, China , Cui, Can Department of Nuclear Medicine - Nanjing First Hospital, Nanjing Medical University - Nanjing, China , Zang, Shimin Department of Nuclear Medicine - Nanjing First Hospital, Nanjing Medical University - Nanjing, China , Qiu, Fan Department of Nuclear Medicine - Nanjing First Hospital, Nanjing Medical University - Nanjing, China , Jia, Ruipeng Department of Urology Surgery - Nanjing First Hospital - Nanjing Medical University - Nanjing, China , Wang, Zizheng Department of Nuclear Medicine - Nanjing First Hospital, Nanjing Medical University - Nanjing, China , Wang, Feng Department of Nuclear Medicine - Nanjing First Hospital, Nanjing Medical University - Nanjing, China
Abstract :
To synthesize 68Ga-Glu-urea-Lys(Ahx)-HBED-CC (68Ga-PSMA-11) with a synthesis module and investigate PET-CT
imaging to monitor PSMA expression during prostate cancer (PCa) progression and tumor growth in mice bearing subcutaneous
PCa xenografs. Method. Te radiochemical purity and stability of 68Ga-PSMA-11 were determined via radio-HPLC. Te PCa cell
lines of diferent PSMA expression levels (PC3, VCAP±, CWR22RV1+, and LNCaP++) were selected to mimic the PCa progression. 68Ga-PSMA-11 biodistribution was studied by dissection method and in vivo imaging with micro PET-CT. Te expression levels
of PSMA in tumor cells and tissues were analyzed by immunofuorescence, fow cytometry, and western blot. Te correlation
between PSMA expression and radio-uptake was also evaluated. 2-PMPA preadministration served as a block group. Results. Te
radiochemical purity of 68Ga-PSMA-11 was 99.6 ± 0.1% and stable in vitro for 2 h. Te equilibrium binding constant (Kd) of 68GaPSMA-11 to LNCaP, CWR22Rv1, PC-3, and VCAP cells was 4.3 ± 0.8 nM, 16.4 ± 1.3 nM, 225.3 ± 20.8 nM, and 125.6 ± 13.1 nM,
respectively. Results of tumor uptake (% ID and % ID/g or % ID/cm3
) of 68Ga-PSMA-11 in biodistribution and micro PET imaging
were LNCaP > CWR22RV1 > PC-3 and VCAP due to diferent PSMA expression levels. It was confrmed by fow cytometry,
western blot, and immunofuorescence. Tumor uptake (% ID/cm3
) of 68Ga-PSMA-11 increased with the tumor anatomical volume
in quadratic polynomial fashion and reached the peak (when tumor volume was 0.5 cm3
) earlier than tumor uptake (% ID). Tumor
uptake (% ID/cm3
) of 68Ga-PSMA-11 based on functional volume correlated well with the PSMA expression in a linear manner
(y = 9.35x+2.59, R2 = 0.8924, and p < 0.0001); however, low dose 2-PMPA causes rapid renal clearance of increased tumor/kidney
uptake of 68Ga-PSMA-11. Conclusions. Te 68Ga-PSMA-11 PET-CT imaging could invasively evaluate PSMA expression during
PCa progression and tumor growth with % ID/cm3 (based on functional volume) as an important index. Low dose 2-PMPA
preadministration might be a choice to decrease kidney uptake of 68Ga-PSMA-11.
