Studies On Molecular Imaging Probe For Targeting Prostate Specific Membrane Antigen

Prostate cancer has shown the greatest increase in the cancer morbidity of adult male in China in the past decade.Early detection,diagnosis and treatment of prostate cancer have become one of the biggest challenges in urological oncology.In recent years,some drugs targeting prostate cancer biomarkers have been developed for clinical use to remarkably improve the level of prostate cancer diagnosis and treatment.At the same time,the rapid development of molecular imaging technology has gradually become an important means for tumor diagnosis.Positron emission computed tomography（PET）has become the most promising imaging technology in modern medical imaging due to its high sensitivity.Compared with other traditional tumor diagnosis methods,it has higher diagnostic efficiency and can truly realize real-time,non-invasive and comprehensive tracking of the evolution process of tumor in vivo.Firstly,meta-analysis was performed to analyze a large number of literatures on molecular imaging probes related to biomarkers of prostate cancers,and it was concluded that the metabolic probes ¹⁸F-FECH and ¹⁸F-NaF were widely used in the diagnosis of advanced prostate cancers.Meanwhile,there were differences in the efficacy of ¹⁸F-NaF and ¹⁸F-FECH in the diagnosis of bone metastasis,lymph node metastasis and biochemical recurrence of middle and advanced prostate cancers.Secondly,a novel fluorine-18 labeling PSMA-targeting PET imaging probe was designed and synthesized.The fluorine-18 labeling precursor was modified based on the structure of the compound PSMA-617 and the triiodobenzoic acid was introduced to increase the binding affinity of the target probe with PSMA and realize potential PET/CT bi-modal imaging.the probe precursor GLNTGT was radiolabeled by the simple and easy"fluorine-18 one-step labeling method",and the probe ¹⁸F-GLNTGT with higher radioactivity purity and specific activity was obtained.The probe¹⁸F-GLNTGT and fetal bovine serum were incubated for four hours and remained unchanged,which indicates that the probe has good in vitro stability.The results of cell uptake and internalization experiments showed that the cell internalization ability of probe ¹⁸F-GLNTGT in LNCaP-positive cells with high PSMA expression was2.4～2.6 times of that in the PC-3 negative cells with low PSMA expression（P<0.05）,indicating that ¹⁸F-GLNTGT has good tumor-targeting specificity.In the competitive binding experiment with PSMA,the K_ivalue of the probe ¹⁸F-GLNTGT was 0.49nM（95%CI:0.35-0.69 nM）,suggesting that the probe ¹⁸F-GLNTGT had a good binding affinity to PSMA.Although the probe precursor GLNTGT is concentration-dependent during in vitro CT imaging,the target probe ¹⁸F-GLNTGT has good tumor-targeting specificity and a long retention time in PSMA-positive LNCaP tumors.This indicated that ¹⁸F-GLNTGT was still a promising PET probe for targeted imaging of PSMA.