Radiation dosimetry and biodistribution in monkey and man of 11C-PBR28:: A PET radioligand to image inflammation
Radiation dosimetry and biodistribution in monkey and man of 11C-PBR28:: A PET radioligand to image inflammation
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DOI：
10.2967/jnumed.107.044842
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发表时间：
2007-12-01
影响因子：
9.3
通讯作者：
Innis, Robert B.
中科院分区：
文献类型：
--
作者：
Brown, Amira K.;Fujita, Masahiro;Innis, Robert B.
C-11-PBR 28（[甲基-C-11] N-乙酰基-N-（2-甲氧基苄基）-2-苯氧基-5-吡啶胺）是新近开发的脑内苯二氮卓受体（PBRs）显像剂。本研究的目的是根据猴子和人类的生物分布数据估计C-11-PBR 28的人体辐射剂量。此外，我们扫描了1名人类受试者，他偶然表现得好像他缺乏PBR结合蛋白。研究方法：在7名健康人（651 +/-111MBq）和2名恒河猴（370 +/-59.9MBq）中静脉推注施用C-11-PBR 28后获得全身PBR图像。用PK 11195（10.7 mg/kg静脉注射）受体阻断后，对1只猴进行扫描。结果如下：对于典型受试者（受试者1 - 6），暴露量最高的3个器官是PBR密度较高的器官（肾、脾和肺），有效剂量为6.6 mu Sv/MBq。异常受试者（受试者7）在这3个器官中的摄取减少60% - 90%，导致有效剂量降低28%。对于具有高PBR密度的器官，基线猴扫描中的活性大于人类中的活性。因此，猴生物分布数据将人体有效剂量高估了60%。接受受体阻滞的猴的总体分布在定性上与不寻常的人类受试者（受试者7）相似，肺、肾和脾暴露量降低。结论：C-11-PBR 28的有效剂量适中，与其他几种C-11-放射性配体相似。罕见的人类受试者和受体阻断的猴子缺乏受体结合，减少了对高PER密度器官的暴露，并增强了排泄和代谢途径的吸收。
C-11-PBR28 ([methyl-C-11]N-acetyl-N-(2-methoxybenzyl)-2phenoxy-5-pyridinamine) is a recently developed radioligand to image peripheral benzodiazepine receptors (PBRs) in brain. The aim of this study was to estimate the human radiation doses of C-11-PBR28 based on biodistribution data in monkeys and humans. In addition, we scanned 1 human subject who fortuitously behaved as if he lacked the PBR binding protein. Methods: Whole-body PBR images were acquired after intravenous bolus administration of C-11-PBR28 in 7 healthy humans (651 +/- 111 MBq) and 2 rhesus monkeys (370 +/- 59.9MBq). One monkey was scanned after receptor blockade with PK 11195 (10.7 mg/kg intravenously). Results: For typical subjects (subjects 1 - 6), the 3 organs with highest exposure were those with the high PBR densities (kidneys, spleen, and lungs), and the effective dose was 6.6 mu Sv/MBq. The unusual subject (subject 7) had 60% - 90% less uptake in these 3 organs, resulting in 28% lower effective dose. The activity in the baseline monkey scans was greater than that in humans for organs with high PBR densities. For this reason, the human effective dose was overestimated by 60% with monkey biodistribution data. The monkey with receptor blockade had an overall distribution qualitatively similar to that of the unusual human subject (subject 7), with decreased exposure to lungs, kidney, and spleen. Conclusion: The effective dose of C-11-PBR28 was modest and was similar to that of several other C-11-radioligands. Lack of receptor binding in the unusual human subject and in the monkey with receptor blockade decreased exposure to organs with high PER densities and enhanced uptake in excretory and metabolic pathways.