Department of Nuclear Medicine, Erasmus MC Rotterdam, Rotterdam, The Netherlands.
J Nucl Med. 2010 Jun;51(6):973-7. doi: 10.2967/jnumed.109.074310. Epub 2010 May 19.
We determined the renal radiation dose of a series of (111)In-labeled peptides using animal SPECT. Because the animals' health deteriorated, renal toxicity was assessed.
Wild-type and megalin-deficient mice were imaged repeatedly at 3- to 6-wk intervals to quantify renal retention after injection of 40-50 MBq of (111)In-diethylenetriaminepentaacetic acid-labeled peptides (octreotide, exendin, octreotate, neurotensin, and minigastrin analogs), and the absorbed kidney radiation doses were estimated. Body weight, renal function parameters, and renal histology were determined at 16-20 wk after the first scan and compared with those in naive animals.
Because of high renal retention, (111)In-diethylenetriaminepentaacetic acid-exendin-4 scans resulted in a 70-Gy kidney radiation dose in wild-type mice. Megalin-deficient kidneys received 20-40 Gy. The other peptides resulted in much lower renal doses. Kidney function monitoring indicated renal damage in imaged animals.
Micro-SPECT enables longitudinal studies in 1 animal. However, long-term nephrotoxic effects may be induced after high renal radiation doses, even with (111)In-labeled radiotracers.
我们使用动物 SPECT 确定了一系列(111)In 标记肽的肾脏辐射剂量。由于动物健康状况恶化,因此评估了肾毒性。
重复对野生型和巨球蛋白缺乏型小鼠进行成像,在注射 40-50 MBq(111)In-二乙三胺五乙酸标记的肽(奥曲肽、exendin、奥曲肽、神经降压素和 minigastrin 类似物)后,以定量评估肾脏保留,并估计肾脏吸收的辐射剂量。在第一次扫描后 16-20 周,测定体重、肾功能参数和肾脏组织学,并与未接受扫描的动物进行比较。
由于肾脏保留率高,(111)In-二乙三胺五乙酸-exendin-4 扫描导致野生型小鼠的肾脏辐射剂量为 70Gy。巨球蛋白缺乏型肾脏的辐射剂量为 20-40Gy。其他肽导致的肾脏剂量要低得多。肾功能监测表明,接受扫描的动物的肾脏受损。
微 SPECT 可在 1 只动物中进行纵向研究。然而,即使使用(111)In 标记的放射性示踪剂,高肾脏辐射剂量也可能导致长期的肾毒性作用。