Doot Robert K, Dubroff Jacob G, Scheuermann Joshua S, Labban Kyle J, Cai Jenny, Hsieh Chia-Ju, Li Shihong, Lee Hsiaoju, Schubert Erin K, Hou Catherine, Sheffer Regan, Schmitz Alexander, Xu Kuiying, Mach Robert H
Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
EJNMMI Phys. 2018 Oct 8;5(1):21. doi: 10.1186/s40658-018-0219-6.
[F]Fluortriopride (FTP) was developed as a dopamine D3-selective radiotracer, thought to be important to neurobiological reward pathways and implicated in drug addiction, Parkinson's disease, and schizophrenia. Preclinical radiation dosimetry studies found the gallbladder wall received the highest dose. A gallbladder dose reduction intervention was simulated using a novel reduction model for healthy adults following fatty-meal consumption. The goals of this study were to assess whole body FTP human dosimetry and determine the feasibility of reducing absorbed dose to the gallbladder wall.
Effective dose without a fatty meal was 0.022 ± 0.002 mSv/MBq (± standard deviation) with highest organ dose of 0.436 ± 0.178 mSv/MBq to the gallbladder wall (n = 10). Predicted gallbladder dose reduction with fatty meal consumed was 67.4% (n = 10). Meal consumption by four repeat volunteers decreased average gallbladder dose by 71.3% (n = 4) compared to the original ten volunteers.
Observed effective doses were adequately low to continue studying FTP uptake in humans. Validated dosimetry simulations indicate up to a 71% reduction in gallbladder dose can be achieved by employing intrinsic physiology to contract the gallbladder via fatty meal ingestion. This methodology for predicting gallbladder absorbed dose reduction from fatty meal consumption can be applied to other radiopharmaceuticals and radiotherapies.
氟哌三嗪(FTP)被开发为一种多巴胺D3选择性放射性示踪剂,被认为对神经生物学奖励途径很重要,并与药物成瘾、帕金森病和精神分裂症有关。临床前辐射剂量学研究发现胆囊壁接受的剂量最高。使用一种针对健康成年人在食用脂肪餐后的新型减少模型模拟了胆囊剂量减少干预。本研究的目的是评估全身FTP人体剂量学,并确定降低胆囊壁吸收剂量的可行性。
未食用脂肪餐时的有效剂量为0.022±0.002 mSv/MBq(±标准差),胆囊壁的最高器官剂量为0.436±0.178 mSv/MBq(n = 10)。食用脂肪餐后预测的胆囊剂量减少为67.4%(n = 10)。与最初的10名志愿者相比,4名重复志愿者食用脂肪餐后平均胆囊剂量降低了71.3%(n = 4)。
观察到的有效剂量足够低,可以继续研究FTP在人体中的摄取情况。经过验证的剂量学模拟表明,通过食用脂肪餐利用内在生理机制使胆囊收缩,可使胆囊剂量降低多达71%。这种预测食用脂肪餐导致胆囊吸收剂量减少的方法可应用于其他放射性药物和放射治疗。