未经证实:前列腺特异性膜抗原(PSMA)-正电子发射断层扫描(PET)指导前列腺癌(PrCa)的转移定向放疗(MDRT)。然而,其作为MDRT后治疗反应评估工具的价值尚不清楚.重要的是,对于放疗(RT)改变PSMA基因(叶酸水解酶1;FOLH1)表达的潜力了解有限.
UNASSIGNED:我们回顾了一系列11例接受MDRT治疗的寡转移PrCa(25个转移部位)的男性患者,然后在继发性复发时用18F-DCFPyL(PSMA)PET重新分期。在人野生型雄激素敏感型(LNCap)中,通过qPCR和免疫印迹检查了RT对PSMA蛋白和mRNA水平的急性影响,去势抗性(22RV1)和去势抗性神经内分泌(PC3和DU145)PrCa细胞系。用免疫组织化学分析异种移植肿瘤。Further,我们检查了未经处理和辐照的耐辐射(RR)22RV1(22RV1-RR)和DU145(DU145-RR)细胞以及高剂量RT后存活的异种移植物中的PSMA表达。
未经证实:大多数MDRT治疗的病变显示缺乏PSMA-PET/CT亲和力,提示即使在低生物有效剂量(BED)MDRT后也有治疗反应。我们观察到在人类标本和异种移植肿瘤中PSMA表达的高度异质性相似。PSMA在LNCap和22RV1细胞和肿瘤中高度表达,但在神经内分泌PC3和DU145模型中不表达。单个级分RT引起可检测到的PSMA蛋白减少,但在LNCap细胞中mRNA水平没有减少,并且在其他细胞系的组织培养或异种移植物中没有显着改变PSMA蛋白或mRNA水平。然而,放射性抗性22RV1-RR细胞和肿瘤显示PSMA转录物和蛋白质表达明显低于其亲本对应物。
UNASSIGNED:PSMA-PET可能是评估低聚转移性PrCa的RT反应的有前途的工具。然而,未来对这一概念的系统研究应认识到前列腺肿瘤中PSMA表达的高度异质性,以及肿瘤在RT治疗过程中PSMA表达丢失的风险.
UNASSIGNED: Prostate Specific Membrane Antigen (PSMA) - positron emission tomography (PET) guides metastasis-directed radiotherapy (MDRT) in prostate cancer (PrCa). However, its value as a treatment response assessment tool after MDRT remains unclear. Importantly, there is limited understanding of the potential of radiotherapy (RT) to alter PSMA gene (folate hydrolase 1; FOLH1) expression.
UNASSIGNED: We reviewed a series of 11 men with oligo-metastatic PrCa (25 metastasis sites) treated with MDRT before re-staging with 18F-DCFPyL (PSMA) PET upon secondary recurrence. Acute effects of RT on PSMA protein and mRNA levels were examined with qPCR and immunoblotting in human wild-type androgen-sensitive (LNCap), castrate-resistant (22RV1) and castrate-resistant neuroendocrine (PC3 and DU145) PrCa cell lines. Xenograft tumors were analyzed with immunohistochemistry. Further, we examined PSMA expression in untreated and irradiated radio-resistant (RR) 22RV1 (22RV1-RR) and DU145 (DU145-RR) cells and xenografts selected for survival after high-dose RT.
UNASSIGNED: The majority of MDRT-treated lesions showed lack of PSMA-PET/CT avidity, suggesting treatment response even after low biological effective dose (BED) MDRT. We observed similar high degree of heterogeneity of PSMA expression in both human specimens and in xenograft tumors. PSMA was highly expressed in LNCap and 22RV1 cells and tumors but not in the neuroendocrine PC3 and DU145 models. Single fraction RT caused detectable reduction in PSMA protein but not in mRNA levels in LNCap cells and did not significantly alter PSMA protein or mRNA levels in tissue culture or xenografts of the other cell lines. However, radio-resistant 22RV1-RR cells and tumors demonstrated marked decrease of PSMA transcript and protein expression over their parental counterparts.
UNASSIGNED: PSMA-PET may be a promising tool to assess RT response in oligo-metastatic PrCa. However, future systematic investigation of this concept should recognize the high degree of heterogeneity of PSMA expression within prostate tumors and the risk for loss of PSMA expression in tumor surviving curative courses of RT.