Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
J Nucl Med. 2013 Sep;54(9):1551-6. doi: 10.2967/jnumed.112.118760. Epub 2013 Aug 15.
Effective anticancer therapy induces tumor cell death through apoptosis. Noninvasive monitoring of apoptosis during therapy may provide predictive outcome information and help tailor treatment. A caspase-3-specific imaging radiotracer, (18)F-(S)-1-((1-(2-fluoroethyl)-1H-[1,2,3]-triazol-4-yl)methyl)-5-(2(2,4-difluorophenoxymethyl)-pyrrolidine-1-sulfonyl)isatin ((18)F-ICMT-11), has been developed for use in PET studies. We report the safety, biodistribution, and internal radiation dosimetry profiles of (18)F-ICMT-11 in 8 healthy human volunteers.
(18)F-ICMT-11 was intravenously administered as a bolus injection (mean ± SD, 159 ± 2.75 MBq; range, 154-161 MBq) to 8 healthy volunteers (4 men, 4 women). Whole-body (vertex to mid thigh) PET/CT scans were acquired at 6 time points, up to 4 h after tracer injection. Serial whole blood, plasma, and urine samples were collected for radioactivity measurement and radiotracer stability. In vivo (18)F activities were determined from quantitative analysis of the images, and time-activity curves were generated. The total numbers of disintegrations in each organ normalized to injected activity (residence times) were calculated as the area under the curve of the time-activity curve, normalized to injected activities and standard values of organ volumes. Dosimetry calculations were then performed using OLINDA/EXM 1.1.
Injection of (18)F-ICMT-11 was well tolerated in all subjects, with no serious tracer-related adverse events reported. The mean effective dose averaged over both men and women was estimated to be 0.025 ± 0.004 mSv/MBq (men, 0.022 ± 0.004 mSv/MBq; women, 0.027 ± 0.004 mSv/MBq). The 5 organs receiving the highest absorbed dose (mGy/MBq), averaged over both men and women, were the gallbladder wall (0.59 ± 0.44), small intestine (0.12 ± 0.05), upper large intestinal wall (0.08 ± 0.07), urinary bladder wall (0.08 ± 0.02), and liver (0.07 ± 0.01). Elimination was both renal and via the hepatobiliary system.
(18)F-ICMT-11 is a safe PET tracer with a dosimetry profile comparable to other common (18)F PET tracers. These data support the further development of (18)F-ICMT-11 for clinical imaging of apoptosis.
为了评估新型正电子发射断层扫描（PET）示踪剂（18）F-ICMT-11 的安全性、生物分布和内照射剂量特征，我们在 8 名健康志愿者中进行了此项研究。
志愿者静脉注射（18）F-ICMT-11（159 ± 2.75 MBq；范围 154-161 MBq），随后进行全身（从头顶至大腿中部）PET/CT 扫描，在注射示踪剂后 6 个时间点进行，最长可达 4 小时。采集系列全血、血浆和尿液样本，以测量放射性活度并评估示踪剂的稳定性。使用定量分析图像的方法确定体内（18）F 活度，并生成时间-活性曲线。通过计算时间-活性曲线的曲线下面积，将每个器官的放射性活度归一化为注射的放射性活度（居留时间），并将其归一化为器官体积的标准值，从而计算出器官的总放射性活度。然后使用 OLINDA/EXM 1.1 进行剂量计算。
所有受试者均耐受良好，未报告与示踪剂相关的严重不良事件。男女平均有效剂量估计为 0.025 ± 0.004 mSv/MBq（男性，0.022 ± 0.004 mSv/MBq；女性，0.027 ± 0.004 mSv/MBq）。男女平均吸收剂量最高（mGy/MBq）的 5 个器官分别为胆囊壁（0.59 ± 0.44）、小肠（0.12 ± 0.05）、大肠上部壁（0.08 ± 0.07）、膀胱壁（0.08 ± 0.02）和肝脏（0.07 ± 0.01）。清除途径为肾清除和肝胆系统清除。
（18）F-ICMT-11 是一种安全的 PET 示踪剂，其剂量特征与其他常见的（18）F PET 示踪剂相似。这些数据支持进一步开发（18）F-ICMT-11 用于凋亡的临床成像。
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