放射性核素 177Lu 标记 Tyr3-奥曲肽治疗后监测大鼠肾功能的动态和静态小动物 SPECT。
Dynamic and static small-animal SPECT in rats for monitoring renal function after 177Lu-labeled Tyr3-octreotate radionuclide therapy.
机构信息
Department of Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands.
出版信息
J Nucl Med. 2010 Dec;51(12):1962-8. doi: 10.2967/jnumed.110.080143. Epub 2010 Nov 15.
UNLABELLED
High kidney radiation doses during clinical peptide receptor radionuclide therapy (PRRT) with β-particle-emitting radiolabeled somatostatin analogs will lead to renal failure several months after treatment, urging the coinfusion of the cationic amino acids lysine and arginine to reduce the renal radiation dose. In rat PRRT studies, renal protection by the coadministration of lysine was confirmed by histologic examination of kidney specimens indicating nephrotoxicity. In the current study, we investigated dedicated small-animal SPECT/CT renal imaging in rats to monitor renal function in vivo during follow-up of PRRT, with and without lysine.
METHODS
The following 3 groups of rats were imaged using a multipinhole SPECT/CT camera: controls (group 1) and rats at more than 90 d after therapy with 460 MBq (15 μg) of (177)Lu-DOTA-Tyr(3)-octreotate without (group 2) or with (group 3) a 400-mg/kg lysine coinjection as kidney protection (n ≥ 6 per group). At 90 and 140 d after therapy, static kidney scintigraphy was performed at 2 h after injection of 25 MBq of (99m)Tc-dimercaptosuccinic acid ((99m)Tc-DMSA). In addition, dynamic dual-isotope renography was performed using 50 MBq of (111)In-diethylenetriaminepentaacetic acid ((111)In-DTPA) and 50 MBq of (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG3) at 100-120 d after therapy.
RESULTS
(111)In-DTPA and (99m)Tc-MAG3 studies revealed a time-activity pattern comparable to those in patients, with a peak at 2-6 min followed by a decline of renal radioactivity. Reduced (111)In-DTPA, (99m)Tc-MAG3, and (99m)Tc-DMSA uptake indicated renal damage in group 2, whereas group 3 showed only a decrease of (99m)Tc-MAG3 peak activity. These results indicating nephrotoxicity in group 2 and renal protection in group 3 correlated with levels of urinary protein and serum creatinine and urea and were confirmed by renal histology.
CONCLUSION
Quantitative dynamic dual-isotope imaging using both (111)In-DTPA and (99m)Tc-MAG3 and static (99m)Tc-DMSA imaging in rats is feasible using small-animal SPECT, enabling longitudinal monitoring of renal function. (99m)Tc-MAG3 renography, especially, appears to be a more sensitive marker of tubular function after PRRT than serum chemistry or (99m)Tc-DMSA scintigraphy.
目的
使用多针孔 SPECT/CT 相机对以下 3 组大鼠进行成像：对照组（第 1 组）和治疗后 90 天以上、接受 460 MBq（15μg）（177）Lu-DOTA-Tyr（3）-奥曲肽且未（第 2 组）或与（第 3 组）400mg/kg 赖氨酸共注射以保护肾脏（每组 n≥6）的大鼠。在治疗后 90 和 140 天，在注射 25MBq（99m）Tc-二巯丁二酸（（99m）Tc-DMSA）后 2h 进行静态肾脏闪烁显像。此外，在治疗后 100-120 天，使用 50MBq（111）In-二乙三胺五乙酸（（111）In-DTPA）和 50MBq（99m）Tc-巯基乙酰三甘氨酸（（99m）Tc-MAG3）进行动态双同位素肾图检查。
结果
（111）In-DTPA 和（99m）Tc-MAG3 研究显示出与患者相似的时间-活性模式，在 2-6min 时出现峰值，随后肾放射性下降。第 2 组的（111）In-DTPA、（99m）Tc-MAG3 和（99m）Tc-DMSA 摄取减少表明存在肾毒性，而第 3 组仅表现出（99m）Tc-MAG3 峰值活性降低。这些结果表明第 2 组的肾毒性和第 3 组的肾保护作用与尿蛋白、血清肌酐和尿素水平相关，并通过肾组织学得到证实。
结论
使用小型动物 SPECT 对大鼠进行动态双同位素成像（111）In-DTPA 和（99m）Tc-MAG3 以及静态（99m）Tc-DMSA 成像，使用定量方法是可行的，可实现肾功能的纵向监测。与血清化学或（99m）Tc-DMSA 闪烁显像相比，（99m）Tc-MAG3 肾图，特别是肾小管功能的敏感标志物，似乎在 PRRT 后更有意义。
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