用于人体正电子发射断层显像（PET）成像的放射性示踪剂剂量3'-脱氧-3'-[¹⁸F]氟代胸腺嘧啶核苷（¹⁸F-FLT）的毒理学评估：系列血样的实验室分析及与先前研究的治疗性FLT剂量的比较
Toxicology evaluation of radiotracer doses of 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) for human PET imaging: Laboratory analysis of serial blood samples and comparison to previously investigated therapeutic FLT doses.
作者信息
Turcotte Eric, Wiens Linda W, Grierson John R, Peterson Lanell M, Wener Mark H, Vesselle Hubert
机构信息
Department of Radiology, Division of Nuclear Medicine, University of Washington, Seattle, USA.
Department of Laboratory Medicine, University of Washington, Seattle, USA.
出版信息
BMC Nucl Med. 2007 Jul 3;7:3. doi: 10.1186/1471-2385-7-3.
BACKGROUND
18F-FLT is a novel PET radiotracer which has demonstrated a strong potential utility for imaging cellular proliferation in human tumors in vivo. To facilitate future regulatory approval of 18F-FLT for clinical use, we wished to demonstrate the safety of radiotracer doses of 18F-FLT administered to human subjects, by: 1) performing an evaluation of the toxicity of 18F-FLT administered in radiotracer amounts for PET imaging, 2) comparing a radiotracer dose of FLT to clinical trial doses of FLT.
METHODS
Twenty patients gave consent to a 18F-FLT injection, subsequent PET imaging, and blood draws. For each patient, blood samples were collected at multiple times before and after 18F-FLT PET. These samples were assayed for a comprehensive metabolic panel, total bilirubin, complete blood and platelet counts. 18F-FLT doses of 2.59 MBq/Kg with a maximal dose of 185 MBq (5 mCi) were used. Blood time-activity curves were generated for each patient from dynamic PET data, providing a measure of the area under the FLT concentration curve for 12 hours (AUC12).
RESULTS
No side effects were reported. Only albumin, red blood cell count, hematocrit and hemoglobin showed a statistically significant decrease over time. These changes are attributed to IV hydration during PET imaging and to subsequent blood loss at surgery. The AUC12 values estimated from imaging data are not significantly different from those found from serial measures of FLT blood concentrations (p = 0.66). The blood samples-derived AUC12 values range from 0.232 ng x h/mL to 1.339 ng x h/mL with a mean of 0.802 +/- 0.303 ng x h/mL. This corresponds to 0.46% to 2.68% of the lowest and least toxic clinical trial AUC12 of 50 ng x h/mL reported by Flexner et al (1994). This single injection also corresponds to a nearly 3,000-fold lower cumulative dose than in Flexner's twice daily trial.
CONCLUSION
This study shows no evidence of toxicity or complications attributable to 18F-FLT injected intravenously.
背景
18F-FLT是一种新型正电子发射断层显像（PET）放射性示踪剂，已证明在体内对人类肿瘤细胞增殖成像具有强大的潜在应用价值。为促进18F-FLT未来获得临床使用的监管批准，我们希望通过以下方式证明给予人类受试者放射性示踪剂剂量的18F-FLT的安全性：1）对用于PET成像的放射性示踪剂剂量的18F-FLT的毒性进行评估，2）将FLT的放射性示踪剂剂量与FLT的临床试验剂量进行比较。
方法
20名患者同意接受18F-FLT注射、随后的PET成像和采血。对于每位患者，在18F-FLT PET检查前后多次采集血样。对这些样本进行综合代谢指标、总胆红素、全血细胞和血小板计数检测。使用的18F-FLT剂量为2.59 MBq/kg，最大剂量为185 MBq（5 mCi）。根据动态PET数据为每位患者生成血药浓度-时间曲线，提供12小时内FLT浓度曲线下面积（AUC12）的测量值。
结果
未报告有副作用。只有白蛋白、红细胞计数、血细胞比容和血红蛋白随时间有统计学显著下降。这些变化归因于PET成像期间的静脉补液以及随后手术中的失血。根据成像数据估计的AUC12值与通过FLT血药浓度系列测量得到的值无显著差异（p = 0.66）。血样得出的AUC12值范围为0.232 ng·h/mL至1.339 ng·h/mL，平均值为0.802±0.303 ng·h/mL。这相当于Flexner等人（1994年）报告的最低且毒性最小的临床试验AUC12值50 ng·h/mL 的0.46%至2.68%。这单次注射的累积剂量也比Flexner每日两次的试验低近3000倍。
结论
本研究表明，没有证据显示静脉注射18F-FLT会产生毒性或并发症。
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