Hsiao Ing-Tsung, Lin Kun-Ju, Huang Kuo-Lun, Huang Chin-Chang, Chen Han-Shiuan, Wey Shiaw-Pyng, Yen Tzu-Chen, Okamura Nobuyuki, Hsu Jung-Lung
Department of Nuclear Medicine and Center for Advanced Molecular Imaging and Translation, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Healthy Aging Research Center and Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan.
J Nucl Med. 2017 Sep;58(9):1498-1503. doi: 10.2967/jnumed.116.189126. Epub 2017 Mar 23.
F-THK-5351 is a novel radiotracer that demonstrates high binding selectivity and affinity for tau pathology and exhibits better pharmacokinetics in the living brain than previous THK tau probes. The aim of the present study was to estimate the radiation dose of F-THK-5351 in humans and to compare the clinical radiation dosimetry results to estimations published previously with preclinical data. Serial whole-body PET/CT imaging was performed for 240 min on 12 healthy volunteers after injecting F-THK-5351 (mean administered activity, 377.8 ± 14.0 MBq; range, 340-397 MBq). The bladder and gallbladder were delineated on PET images, and the other organs were delineated on CT images. Voided urine activity was recorded. The decay-corrected and normalized F-THK-5351 activity of 15 source-organ regions as a function of time was entered into the OLINDA/EXM software to calculate the effective dose for each subject following the medical internal radiation dosimetry schema. Overall, the F-THK-5351 injection was well tolerated. The highest mean initial uptake at 10 min after injection was in the liver (11.4% ± 2.0%), lung (5.7% ± 2.1%), intestine (3.4% ± 0.8%), and kidney (1.4% ± 0.3%). The highest mean absorbed dose of radiation was in the gallbladder wall (242.2 ± 105.2 μGy/MBq), upper large intestine (90.0 ± 15.8 μGy/MBq), small intestine (79.5 ± 13.8 μGy/MBq), and liver (55.8 ± 6.1 μGy/MBq). The resultant whole-body effective dose was 22.7 ± 1.3 μSv/MBq. Our results suggest that a routine injection of 370 MBq of F-THK-5351 would lead to an estimated effective dose of 8.4 mSv; hence, F-THK-5351 has a radiation burden similar to that of other commonly used clinical tracers. Our findings in humans were compatible with recently published preclinical dosimetry data extrapolated from mice.
F-THK-5351是一种新型放射性示踪剂，对tau病理表现出高结合选择性和亲和力，并且在活体大脑中比先前的THK tau探针具有更好的药代动力学。本研究的目的是估计F-THK-5351在人体中的辐射剂量，并将临床辐射剂量测定结果与先前发表的基于临床前数据的估计值进行比较。在12名健康志愿者注射F-THK-5351后（平均给药活度，377.8±14.0 MBq；范围，340 - 397 MBq），进行了240分钟的全身PET/CT连续成像。在PET图像上勾勒出膀胱和胆囊，在CT图像上勾勒出其他器官。记录排尿后的尿液活度。将15个源器官区域经衰变校正和归一化的F-THK-5351活度作为时间的函数输入到OLINDA/EXM软件中，以按照医学内照射剂量测定方案计算每个受试者的有效剂量。总体而言，F-THK-5351注射耐受性良好。注射后10分钟时平均初始摄取量最高的部位是肝脏（11.4%±2.0%）、肺（5.7%±2.1%）、肠道（3.4%±0.8%）和肾脏（1.4%±0.3%）。辐射平均吸收剂量最高的部位是胆囊壁（242.2±105.2 μGy/MBq）、上段大肠（90.0±15.8 μGy/MBq）、小肠（79.5±13.8 μGy/MBq）和肝脏（55.8±6.1 μGy/MBq）。由此得出的全身有效剂量为22.7±1.3 μSv/MBq。我们的结果表明，常规注射370 MBq的F-THK-5351将导致估计有效剂量为8.4 mSv；因此，F-THK-5351的辐射负担与其他常用临床示踪剂相似。我们在人体中的研究结果与最近发表的从小鼠外推得到的临床前剂量测定数据一致。
