Department of Urology, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Fukui, 9101193, Japan.
Eur J Nucl Med Mol Imaging. 2011 Jan;38(1):81-9. doi: 10.1007/s00259-010-1613-z. Epub 2010 Sep 29.
The aim of the study was to assess the potential usefulness of 3-deoxy-3-(18)F-fluorothymidine (FLT) as a radiopharmaceutical for imaging the early therapeutic effects of docetaxel (DTX) on tumour proliferation in hormone-refractory prostate cancer (HRPC).
Cells of the androgen-independent human prostate tumour cell line, 22Rv1, were implanted in athymic male mice. Approximately 3 weeks after cell implantation, the mice were treated with DTX or vehicle. Before and after the treatment, the mice were imaged with a microPET-Focus-F120 scanner (Concorde Microsystems, Knoxville, TN, USA) using FLT and (18)F-fluorodeoxyglucose (FDG). Tracer accumulations in the tumours were then analysed and compared with the proliferation activity and apoptotic index of the tumours. In a separate cell study, 22Rv1 cells were treated with DTX, then incubated with FLT or FDG and examined for their tracer uptake.
The microPET imaging showed a significant decrease of FLT uptake in tumours after administration of DTX, while the changes of FDG uptake were minimal. Immunohistochemical analysis of the tumours revealed that the changes of FLT uptake were well correlated with those of proliferation activity but not with the apoptotic index. In vitro studies demonstrated that the significant decrease of FLT uptake in the cells after incubation with DTX correlated with the % S-phase cell fraction, while there were only minimal changes in the prostate-specific antigen concentration of the cell medium and FDG uptake in the cells.
These results indicate that FLT is a promising tracer for monitoring the early effects of anticancer therapy with DTX in patients with HRPC.
本研究旨在评估 3-去氧-3-[18]F-氟代胸腺嘧啶（FLT）作为放射性药物用于检测多西紫杉醇（DTX）对激素难治性前列腺癌（HRPC）肿瘤增殖早期治疗效果的潜在作用。
将雄激素非依赖性人前列腺肿瘤细胞系 22Rv1 细胞植入无胸腺雄性小鼠。细胞植入约 3 周后，用 DTX 或载体处理小鼠。在治疗前后，使用 microPET-Focus-F120 扫描仪（Concorde Microsystems，Knoxville，TN，USA）用 FLT 和（18）F-氟脱氧葡萄糖（FDG）对小鼠进行成像。然后分析肿瘤中的示踪剂积聚，并与肿瘤的增殖活性和凋亡指数进行比较。在一项单独的细胞研究中，用 DTX 处理 22Rv1 细胞，然后用 FLT 或 FDG 孵育，并检查其示踪剂摄取。
microPET 成像显示，DTX 给药后肿瘤中 FLT 摄取明显减少，而 FDG 摄取变化最小。肿瘤的免疫组织化学分析显示，FLT 摄取的变化与增殖活性的变化密切相关，但与凋亡指数无关。体外研究表明，用 DTX 孵育后细胞中 FLT 摄取的显著减少与 S 期细胞分数的百分比相关，而细胞培养基中前列腺特异性抗原浓度和细胞中 FDG 摄取仅有微小变化。
这些结果表明，FLT 是一种很有前途的示踪剂，可用于监测 HRPC 患者接受 DTX 抗癌治疗的早期效果。
