Suppr
超能文献

氘取代的18F-氟甲基-[1,2-2H4]胆碱在健康志愿者体内的生物分布及辐射剂量测定

Biodistribution and radiation dosimetry of deuterium-substituted 18F-fluoromethyl-[1, 2-2H4]choline in healthy volunteers.

作者信息

Challapalli Amarnath, Sharma Rohini, Hallett William A, Kozlowski Kasia, Carroll Laurence, Brickute Diana, Twyman Frazer, Al-Nahhas Adil, Aboagye Eric O

机构信息

Department of Surgery and Cancer, Imperial College London, London, United Kingdom.

出版信息

J Nucl Med. 2014 Feb;55(2):256-63. doi: 10.2967/jnumed.113.129577.

DOI:10.2967/jnumed.113.129577

PMID:24492392

Abstract

UNLABELLED

(11)C-choline and (18)F-fluoromethylcholine ((18)F-FCH) have been used in patients to study tumor metabolic activity in vivo; however, both radiotracers are readily oxidized to respective betaine analogs, with metabolites detectable in plasma soon after injection of the radiotracer. A more metabolically stable FCH analog, (18)F-fluoromethyl-[1,2-(2)H4]choline ((18)F-D4-FCH), based on the deuterium isotope effect, has been developed. We report the safety, biodistribution, and internal radiation dosimetry profiles of (18)F-D4-FCH in 8 healthy human volunteers.

METHODS

(18)F-D4-FCH was intravenously administered as a bolus injection (mean ± SD, 161 ± 2.17 MBq; range, 156-163 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 plasma radiotracer metabolites. Tissue (18)F radioactivities 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 organ volumes. Dosimetry calculations were performed using OLINDA/EXM 1.1.

RESULTS

The injection of (18)F-D4-FCH was well tolerated in all subjects, with no radiotracer-related serious adverse event reported. The mean effective dose averaged over both men and women (± SD) was estimated to be 0.025 ± 0.004 (men, 0.022 ± 0.002; women, 0.027 ± 0.002) mSv/MBq. The 5 organs receiving the highest absorbed dose (mGy/MBq) were the kidneys (0.106 ± 0.03), liver (0.094 ± 0.03), pancreas (0.066 ± 0.01), urinary bladder wall (0.047 ± 0.02), and adrenals (0.046 ± 0.01). Elimination was through the renal and hepatic systems.

CONCLUSION

(18)F-D4-FCH is a safe PET radiotracer with a dosimetry profile comparable to other common (18)F PET tracers. These data support the further development of (18)F-D4-FCH for clinical imaging of choline metabolism.

摘要

未标注

（11）C-胆碱和（18）F-氟甲基胆碱（（18）F-FCH）已用于患者体内研究肿瘤代谢活性；然而，这两种放射性示踪剂都很容易氧化为各自的甜菜碱类似物，注射放射性示踪剂后不久血浆中就能检测到代谢物。基于氘同位素效应，已开发出一种代谢更稳定的FCH类似物，即（18）F-氟甲基-[1,2-（2）H4]胆碱（（18）F-D4-FCH）。我们报告了8名健康人类志愿者中（18）F-D4-FCH的安全性、生物分布和体内辐射剂量学特征。

方法

将（18）F-D4-FCH以静脉推注的方式（平均±标准差，161±2.17 MBq；范围，156 - 163 MBq）给予8名健康志愿者（4名男性，4名女性）。在注射示踪剂后长达4小时的6个时间点进行全身（头顶至大腿中部）PET/CT扫描。采集系列全血、血浆和尿液样本用于放射性测量及血浆放射性示踪剂代谢物分析。通过图像定量分析确定组织中的（18）F放射性，并生成时间-活性曲线。将每个器官中归一化到注射活度（驻留时间）的总衰变数计算为时间-活性曲线下面积，该曲线已归一化到注射活度和标准器官体积。使用OLINDA/EXM 1.1进行剂量学计算。

结果

所有受试者对（18）F-D4-FCH注射耐受性良好，未报告与放射性示踪剂相关的严重不良事件。男性和女性的平均有效剂量（±标准差）估计为0.025±0.004（男性，0.022±0.002；女性，0.027±0.002）mSv/MBq。吸收剂量最高的5个器官（mGy/MBq）为肾脏（0.106±0.03）、肝脏（0.094±0.03）、胰腺（0.066±0.01）、膀胱壁（0.047±0.02）和肾上腺（0.046±0.01）。通过肾脏和肝脏系统排泄。