Kesner Adam L, Hsueh Wei-Ann, Czernin Johannes, Padgett Henry, Phelps Michael E, Silverman Daniel H S
Molecular and Medical Pharmacology, Ahmanson Biological Imaging Division, UCLA Medical Center, Los Angeles, CA 90095-6942, USA.
Mol Imaging Biol. 2008 Nov-Dec;10(6):341-8. doi: 10.1007/s11307-008-0160-5. Epub 2008 Aug 5.
Radiation dosimetry assessment often begins with measuring pharmaceutical biodistribution in rodents. The traditional approach to dosimetry in rodents involves a radioassay ex vivo of harvested organs at different time points following administration of the radiopharmaceutical. The emergence of small-animal positron emission tomography (PET) presents the opportunity for an alternative method for making radiodosimetry estimates previously employed only in humans and large animals. In the current manuscript, normal-tissue absorbed dose estimates for the 18F-labeled chemotherapy agent [18F]5-fluorouracil ([18F]5-FU) were derived by PET imaging- and by tissue harvesting-based methods in rats.
Small-animal PET data were acquired dynamically for up to 2 h after injection of [18F]5-FU in anesthetized rats (n=16). Combined polynomial and exponential functions were used to model the harvesting-based and imaging-based time-activity data. The measured time-activity data were extrapolated to modeled (i.e., Standard Man) human organs and human absorbed doses calculated.
Organ activities derived by imaging-based and by harvesting-based methods were highly correlated (r>0.999) as were the projected human dosimetry estimates across organs (r=0.998) obtained with each method. The tissues calculated to receive highest radiation dose by both methods were related to routes of excretion (bladder wall, liver, and intestines). The harvesting-based and imaging-based methods yielded effective dose (ED) of 2.94E-2 and 2.97E-2 mSv/MBq, respectively.
Small-animal PET presents an opportunity for providing radiation dose estimates with statistical and logistical advantages over traditional tissue harvesting-based methods.
辐射剂量学评估通常始于测量啮齿动物体内药物的生物分布。传统的啮齿动物剂量学方法是在给予放射性药物后的不同时间点对采集的器官进行离体放射性测定。小动物正电子发射断层扫描（PET）的出现为一种替代方法提供了机会，这种方法以前仅用于人类和大型动物的放射性剂量测定。在当前的手稿中，通过PET成像和基于组织采集的方法在大鼠中得出了18F标记的化疗药物[18F]5-氟尿嘧啶（[18F]5-FU）的正常组织吸收剂量估计值。
在麻醉的大鼠（n = 16）中注射[18F]5-FU后，动态采集小动物PET数据长达2小时。使用组合多项式和指数函数对基于采集和基于成像的时间-活度数据进行建模。将测量的时间-活度数据外推到建模的（即标准人）人体器官，并计算人体吸收剂量。
基于成像和基于采集的方法得出的器官活度高度相关（r>0.999），两种方法获得的各器官预计人体剂量估计值也高度相关（r = 0.998）。两种方法计算得出接受最高辐射剂量的组织都与排泄途径有关（膀胱壁、肝脏和肠道）。基于采集和基于成像的方法得出的有效剂量（ED）分别为2.94E-2和2.97E-2 mSv/MBq。
小动物PET为提供辐射剂量估计提供了机会，与传统的基于组织采集的方法相比，具有统计学和后勤学优势。
