Department of Medicine D, Experimental Nephrology, University of Münster, Münster, Germany.
J Nucl Med. 2010 Oct;51(10):1644-52. doi: 10.2967/jnumed.110.078550. Epub 2010 Sep 16.
We propose (18)F-FDG PET as a method to monitor acute rejection of allogeneic renal transplants in a rat model.
Allogeneically transplanted (aTX) rats (binephrectomized Lewis-brown Norway to Lewis) served as the renal transplant model. aTX rats treated with cyclosporine A (CSA) served as a therapy monitoring group. Healthy control rats, rats with acute CSA nephrotoxicity, rats with acute tubular necrosis, syngeneically transplanted (sTX) rats, and aTX rats treated with CSA since postoperative day 0 served as controls. After surgery, renal glucose metabolism was assessed in vivo serially up to postoperative day 7 by performing small-animal PET 3 h after intravenous injection of 30 MBq of (18)F-FDG. Mean radioactivity (cps/mm(3) of tissue) was measured and the percentage injected dose calculated. Results were confirmed by histologic, functional, and autoradiographic analysis.
Renal (18)F-FDG uptake was significantly elevated at postoperative day 4 in aTX rats, when compared with control, sTX, acute tubular necrosis, or CSA-treated rats (P < 0.05). In vivo (18)F-FDG uptake correlated with the results of autoradiography and with inflammatory infiltrates observed on histologic examination. Notably, (18)F-FDG PET assessed the response to therapy 48 h earlier than the time at which serum creatinine decreased and when histologic examination still showed signs of allograft rejection. In aTX rats, the CSA-susceptible graft infiltrate was dominated by activated cytotoxic T cells and monocytes/macrophages.
(18)F-FDG PET is an option to noninvasively assess early response to therapy in rat renal allograft rejection.
我们提出（18）F-FDG PET 作为监测同种异体肾移植大鼠模型急性排斥反应的方法。
将同种异体移植（aTX）大鼠（双肾切除的 Lewis-棕褐色挪威到 Lewis）作为肾移植模型。接受环孢素 A（CSA）治疗的 aTX 大鼠作为治疗监测组。健康对照大鼠、急性 CSA 肾毒性大鼠、急性肾小管坏死大鼠、同基因移植（sTX）大鼠以及术后第 0 天开始接受 CSA 治疗的 aTX 大鼠作为对照组。手术后，通过在静脉注射 30MBq（18）F-FDG 后 3 小时进行小动物 PET，在体内连续评估术后第 7 天的肾葡萄糖代谢。测量放射性活度（组织中 cps/mm(3)）并计算注射剂量的百分比。结果通过组织学、功能和放射自显影分析进行确认。
与对照、sTX、急性肾小管坏死或 CSA 治疗的大鼠相比，aTX 大鼠在术后第 4 天肾（18）F-FDG 摄取明显升高（P<0.05）。体内（18）F-FDG 摄取与放射自显影结果以及组织学检查观察到的炎症浸润相关。值得注意的是，（18）F-FDG PET 评估治疗反应的时间比血清肌酐降低的时间早 48 小时，并且组织学检查仍显示移植物排斥的迹象。在 aTX 大鼠中，CSA 易感移植物浸润主要由激活的细胞毒性 T 细胞和单核细胞/巨噬细胞组成。
（18）F-FDG PET 是一种非侵入性评估大鼠肾移植排斥反应早期治疗反应的选择。
