Preclinical Evaluation of a Fluorine-18 Labeled Probe for the Detection of the Expression of PSMA Level in Cancer

氟-18标记探针检测癌症中PSMA表达水平的临床前评价

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Abstract

Prostate-specific membrane antigen (PSMA) is a prospect biomarker for the treatment of prostate cancer. Meanwhile, positron emission tomography (PET) is being developed as a significant imaging modality in cancer diagnosis. A new PET probe Glu-ureido-Lys-naphthylalanine-tranexamic acid-Gly(AMBF(3))-triiodobenzoic acid ((18)F-GLNTGT) was radiosynthesized by a one-step (18)F-labeled method. (18)F-GLNTGT was obtained with a radioactivity yield (RCY) of 12.16 ± 6.4% and a good radiochemical purity (RCP > 96%). The cell uptakes of (18)F-GLNTGT were determined to be 15.9 ± 0.43% ID and 9.47 ± 1.26% ID at 15 min in LNCaP cells and PC-3 cells, respectively. The cell internalization of (18)F-GLNTGT was determined to be 12.89 ± 0.94% ID and 5.34 ± 0.15% ID at 15 min in LNCaP cells and PC-3 cells, respectively. It is suggested that the probe has good specificity targeting PSMA. From the results of (18)F-GLNTGT binding affinity with PSMA, it has a higher affinity and a K (i) value of 0.49 nM (95% confidence interval (CI): 0.35-0.67 nM). In PET imaging, (18)F-GLNTGT showed the highest tumor uptake of 3.51 ± 0.15% ID/g at 45 min and the maximum tumor/muscle (T/M(max)) ratio of 3.68 ± 0.29 at 60 min post-injection (p.i.) in LNCaP tumors. The control probe (18)F-AlF-NOTA-RGD(2) presented the highest tumor uptake of 4.2 ± 0.54% ID/g at 7.5 min and the T/M(max) ratio of 2.72 ± 0.63 at 45 min p.i. in LNCaP tumors. The results showed that the probe has a higher tumor/muscle ratio compared with the control probe (18)F-AlF-NOTA-RGD(2). Although the probe (18)F-GLNTGT has some limitations for CT signal detection both in cells and in vivo, it is still a promising PET probe for targeting PSMA membrane protein.

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