Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1 Naka-cho, Itabashi-ku, Tokyo 173-0022, Japan.
Ann Nucl Med. 2013 Apr;27(3):285-96. doi: 10.1007/s12149-013-0685-9. Epub 2013 Feb 13.
We investigated the whole-body biodistributions and radiation dosimetry of five (11)C-labeled and one (18)F-labeled radiotracers in human subjects, and compared the results to those obtained from murine biodistribution studies.
The radiotracers investigated were (11)C-SA4503, (11)C-MPDX, (11)C-TMSX, (11)C-CHIBA-1001, (11)C-4DST, and (18)F-FBPA. Dynamic whole-body positron emission tomography (PET) was performed in three human subjects after a single bolus injection of each radiotracer. Emission scans were collected in two-dimensional mode in five bed positions. Regions of interest were placed over organs identified in reconstructed PET images. The OLINDA program was used to estimate radiation doses from the number of disintegrations of these source organs. These results were compared with the predicted human radiation doses on the basis of biodistribution data obtained from mice by dissection.
The ratios of estimated effective doses from the human-derived data to those from the mouse-derived data ranged from 0.86 to 1.88. The critical organs that received the highest absorbed doses in the human- and mouse-derived studies differed for two of the six radiotracers. The differences between the human- and mouse-derived dosimetry involved not only the species differences, including faster systemic circulation of mice and differences in the metabolism, but also measurement methodologies.
Although the mouse-derived effective doses were roughly comparable to the human-derived doses in most cases, considerable differences were found for critical organ dose estimates and pharmacokinetics in certain cases. Whole-body imaging for investigation of radiation dosimetry is desirable for the initial clinical evaluation of new PET probes prior to their application in subsequent clinical investigations.
我们在人体受试者中研究了五种（11）C 标记和一种（18）F 标记放射性示踪剂的全身生物分布和辐射剂量，并将结果与从鼠类生物分布研究中获得的结果进行比较。
研究的放射性示踪剂为（11）C-SA4503、（11）C-MPDX、（11）C-TMSX、（11）C-CHIBA-1001、（11）C-4DST 和（18）F-FBPA。在每个放射性示踪剂单次推注后，对三名人体受试者进行全身动态正电子发射断层扫描（PET）。在五个床位位置以二维模式采集发射扫描。将感兴趣区域放置在重建的 PET 图像中识别的器官上。使用 OLINDA 程序根据从老鼠中获得的生物分布数据来估计这些源器官的放射性剂量。将这些结果与从老鼠中获得的生物分布数据预测的人类辐射剂量进行比较。
从人体数据得出的估计有效剂量与从老鼠数据得出的估计有效剂量之比范围为 0.86 至 1.88。在六种放射性示踪剂中的两种中，人类和老鼠研究中接受最高吸收剂量的关键器官不同。人类和老鼠衍生的剂量学之间的差异不仅涉及到物种差异，包括老鼠的全身循环更快以及代谢的差异，还涉及到测量方法学。
尽管在大多数情况下，从老鼠衍生的有效剂量与从人体衍生的剂量大致相当，但在某些情况下，关键器官剂量估算和药代动力学存在相当大的差异。在将新的 PET 探针应用于随后的临床研究之前，对其进行初步临床评估时，全身成像对于研究辐射剂量学是理想的。
