唑来膦酸诱导前列腺癌骨转移 [F]FMAU 正电子发射断层成像改变的初步试验。
A Pilot Trial Evaluating Zoledronic Acid Induced Changes in [F]FMAU-Positron Emission Tomography Imaging of Bone Metastases in Prostate Cancer.
机构信息
Karmanos Cancer Institute, Wayne State University, 4233 Hudson Weber Cancer Center, 4100 John R, Detroit, MI, 48201, USA.
University of California San Francisco, Fresno, CA, USA.
出版信息
Mol Imaging Biol. 2017 Dec;19(6):810-816. doi: 10.1007/s11307-017-1057-y.
PURPOSE
We conducted a pilot trial utilizing [F]FMAU [1-(2'-deoxy-2'-[F]fluoro-β-D-arabinofuranosyl thymine] as a tumor tracer in positron emission tomography (PET) and evaluated its reproducibility, and changes in maximum and peak standardized uptake value (SUVmax and SUVpeak) with zoledronic acid treatment in castrate resistant prostate cancer (CRPC) patients with bone metastases (BM).
PROCEDURES
Eligible patients had CRPC with radiographic evidence of BM and creatinine clearance >30 ml/min. Two baseline [F]FMAU-PET scans (about 1 week apart, range 2-12 days) were obtained for testing reproducibility. Zoledronic acid 4 mg was infused over 15 min within 1 week after second scan and a third PET scan was obtained 7 days later. The bony lesion with the highest uptake on the first scan was compared with later scans. Bone turnover markers and prostate-specific antigen (PSA) were obtained pre- and post-therapy. PET response was defined as decline in SUVmean of ≥15 % after zoledronic acid.
RESULTS
Eleven patients were evaluated, median age was 65 years, five were African-American and six were Caucasian, and median PSA level was 36.3 ng/ml (range 1.0-1209.3). Notably, the range of absolute percent SUVmax changes varied between 0.77 and 54.7, and only nine measurements were greater than one (1.09-2.19). Zoledronic acid did not appreciably change FMAU uptake. No clinical response was noted. Urine N-telopeptide (NTx) was markedly decreased in all patients after zoledronic acid and serum bone-specific alkaline phosphatase (BSAP) registered a modest change. Urine NTx correlated more closely with SUV max than serum BSAP.
CONCLUSIONS
FMAU tracer was able to detect bone metastases in CRPC patients but uptake was highly variable in bony lesions. Zoledronic acid did not produce an appreciable change in scans. Future investigations of FMAU tracer as a marker of early response in CRPC is recommended.
目的
我们利用[F]FMAU[1-(2'-去氧-2'-[F]氟代-β-D-阿拉伯呋喃糖基胸腺嘧啶]作为正电子发射断层扫描（PET）中的肿瘤示踪剂进行了一项试验，评估了其在伴有骨转移（BM）的去势抵抗性前列腺癌（CRPC）患者中的可重复性，以及唑来膦酸治疗后最大和峰值标准化摄取值（SUVmax 和 SUVpeak）的变化。
程序
符合条件的患者为 CRPC 患者，有放射性 BM 证据，肌酐清除率>30ml/min。在进行试验前，患者接受了两次[F]FMAU-PET 扫描（相隔约 1 周，范围为 2-12 天），以测试其可重复性。第二次扫描后 1 周内，给予唑来膦酸 4mg，静脉滴注 15 分钟，7 天后再次进行 PET 扫描。第一次扫描中摄取最高的骨病灶与后续扫描进行比较。治疗前后均获得骨转换标志物和前列腺特异性抗原（PSA）。定义 PET 反应为唑来膦酸治疗后 SUVmean 下降≥15%。
结果
共评估了 11 例患者，中位年龄为 65 岁，5 例为非裔美国人，6 例为白人，中位 PSA 水平为 36.3ng/ml（范围为 1.0-1209.3）。值得注意的是，SUVmax 绝对值变化的范围为 0.77-54.7，只有 9 次测量值大于 1（1.09-2.19）。唑来膦酸并未明显改变 FMAU 的摄取。未观察到临床反应。所有患者在使用唑来膦酸后尿 N-末端肽（NTx）显著降低，而血清骨特异性碱性磷酸酶（BSAP）略有变化。尿 NTx 与 SUVmax 的相关性优于血清 BSAP。
结论
FMAU 示踪剂能够检测 CRPC 患者的骨转移，但骨病灶的摄取差异很大。唑来膦酸治疗后扫描未见明显变化。建议进一步研究 FMAU 示踪剂作为 CRPC 早期反应的标志物。
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