以大鼠生物分佈評估正腎上腺素轉運體造影劑碘－123-MIPP輻射劑量

Radiation Dose Assessment of a Norepinephrine Transporter Imaging Agent 123I-MIPP Using Rat Biodistribution Data

高弘俊(Hung-Chun Kao) ； 劉學絢(Hsueh-Hsuan Liu) ； 李世瑛(Shih-Yin Lee) ； 張家榮(Chia-Jung Chang) ； 吳國宏(Kuo-Hung Wu) ； 張剛瑋(Kang-Wei Chang) ； 姚正祥(Cheng-Xiang Yao) ； 吳杰(Jay Wu)

《核子醫學雜誌》 19卷3期 (2006/09) Pp. 167-173

https://doi.org/10.6332/ANMS.1903.006

摘要

背景：單光子放射電腦斷層造影劑碘－123-(R)-N-methyl-3-(2-iodophenoxy)-3-phenylpropanamine（碘－123-MIPP）是針對腦正腎上腺素轉運體所研發的核醫藥物，有助於憂鬱症等神經精神疾病的研究及診斷。本研究為評估碘－123-MIPP應用於人體造影時可能造成的輻射劑量，實驗蒐集大鼠的生物分佈數據，以評估該藥物在人體重要器官吸收劑量及全身有效劑量等，以提供必要的輻射安全考量。
方法：共18隻Sprague-Dawley品系雄性大鼠分別注射碘－123-MIPP，以3隻為一組分別在5分鐘、30分鐘、1小時、2小時、4小時和24小時後犧牲，計算各器官與組織在不同時間點的注射劑量百分比，以梯形法與放射性物理衰變計算放射性藥物在大鼠體內的滯留時間，並藉由體內劑量評估程式MIRDOSE 3.0計算70公斤成人器官吸收劑量與有效劑量。
結果：碘－123-MIPP能通過血腦屏障，注射30分鐘後腦部攝取量最高，每公克組織有0.36%注射劑量。甲狀腺為輻射劑量最高的器官，每百萬貝克(MBq)造成吸收劑量0.24毫戈雷(mGy)。有效劑量則為每百萬貝克(MBq)造成0.038毫西弗(mSv)。
結論：利用大鼠生物分佈數據評估碘－123 MIPP在人體造成的輻射劑量與其他碘－123核醫造影劑的劑量相當。預估之劑量值為未來人體實驗輻射安全考量提供了參考依據。

關鍵字

正腎上腺素轉運體 ； 碘－123-MIPP ； 生物分佈 ； 輻射劑量

並列摘要

Background: (R)-N-methyl-3-(2-bromophenoxy)-3-phenylpropanamine, 123I-MIPP, has been evaluated as a useful radioligand targeting norepinephrine transporters (NET). To assess the potential feasibility of 123I-MIPP for myocardial or brain NET imaging, determination of radiation doses to individual organs and the whole body caused by 123I-MIPP is essential. In this study, we prepared 123I-MIPP and investigated the distribution of 123I-MIPP in rats. Gathered biodistribution data were used to estimate absorbed and effective dose in human.
Methods: A total of 18 Sprague-Dawley rats was subdivided into 6 groups (3 each) and was sacrificed at 5min, 30min, 1h, 2h, 4h, and 24h post injection of 1.85 MBq 123I-MIPP, respectively. Organs of interest were removed and weighed. Radioactivities of those organs or tissues were measured to calculate the percent injection dose per gram (%ID/g) and per organ (%ID/organ). Absorbed dose for a 70-kg adult was computed according to the MIRD schema with MIRDOSE 3 software.
Results: Peak uptake in brain (0.36 %ID/g) was found at 30min to 1h post tracer administration. Lung had the highest %ID/g during the first 2h. The residence times in 18 organs were calculated as the trapezoidal sum of the observed data plus physical decay. Organ with the highest radiation dose was the thyroid, 0.24mGy/MBq. The effective dose in man was estimated as 0.038mSv/MBq.
Conclusion: Based on the rat biodistribution data and MIRD software, the present study calculated the radiation dose of 123I-MIPP in human subjects. The assessed radiation dose in man was comparable to those of the other 123I imaging agents. The dose-limiting organ was found in the thyroid gland. According to the US federal regulations for studies under Radiation Drug Research Committee (RDRC), the maximum allowable single study dose is 200 MBq, as estimated in this work.

並列關鍵字

norepinephrine transporter ； 123I-MIPP ； biodistribution ； radiation dosimetry