Abstract
Objective 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 xenografts. Method The radiochemical purity and stability of 68Ga-PSMA-11 were determined via radio-HPLC. The PCa cell lines of different 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. The expression levels of PSMA in tumor cells and tissues were analyzed by immunofluorescence, flow cytometry, and western blot. The correlation between PSMA expression and radio-uptake was also evaluated. 2-PMPA preadministration served as a block group. Results The radiochemical purity of 68Ga-PSMA-11 was 99.6 ± 0.1% and stable in vitro for 2 h. The equilibrium binding constant (Kd) of 68Ga-PSMA-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 different PSMA expression levels. It was confirmed by flow cytometry, western blot, and immunofluorescence. 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 The 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.
Highlights
In spite of great efforts and recent advances in early diagnosis and surgical intervention, prostate cancer (PCa) remains the most commonly diagnosed cancer and second leading cause of cancer-related death in men over 40 years [1]
The radiochemical yield of Gallium-68 Prostate-specific membrane antigen (PSMA) (68Ga)-PSMA-11 from the synthesis module was more than 95%
There were two peaks with averaged retention time of 11.1 min and 11.5 min, which was corresponding to different diastereomers of 68GaPSMA-11
Summary
In spite of great efforts and recent advances in early diagnosis and surgical intervention, prostate cancer (PCa) remains the most commonly diagnosed cancer and second leading cause of cancer-related death in men over 40 years [1]. Therapeutic effects for localized PCa in patients of stages I, II, and III are relatively fine by standard employed treatments. PCa patients with relapse, distant metastasis (stage IV), and high risk of PCa progression and/or death are all considered as advanced PCa [2, 3]. Most of them become resistant to hormonal approach and developed a metastatic castration-resistant prostate cancer (mCRPC) shortly after androgen deprivation therapy. Most widely used for mCRPC, is of decreasing therapeutic efficacy due to lack of specificity and associated side effects. It becomes a main challenge to effectively diagnose and select appropriate treatment options for advanced PCa and mCRPC
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
