From the Nuclear Medicine Department, Zibo Central Hospital, Shandong University, Zibo, Shandong, PR China.
Exp Clin Transplant. 2020 Jun;18(3):368-374. doi: 10.6002/ect.2019.0346.
It has been reported that CXCR3 is related to inflammatory cell infiltration. The purpose of this study was to investigate iodine-125-labeled CXCL10, a ligand of CXCR3, as a tracer targeting CXCR3 to detect acute rejection in a mouse skin transplant model.
The isograft and allograft skin models were established with BALB/c and C57BL/6 mouse skin, respectively, as donors and BALB/c mice as recipients. We used reverse transcriptase-polymerase chain reaction and immunochemistry staining to test CXCR3 expression. ¹²⁵I-labeled CXCL10 was produced with the iodogenic method. Allograft/isograft mice were examined with whole body autoradiography and ex vivo biodistribution after tail vein injection of ¹²⁵I-labeled CXCL10 on day 8 posttransplant.
CXCR3 expression was higher in allograft tissue than in isograft control. ¹²⁵I-labeled CXCL10 was prepared with high specificity and affinity. Biodistribution results showed higher ¹²⁵I-labeled CXCL10 uptake in allograft tissue. The target-to-nontarget ratio was 3.01 ± 0.25 at 24 hours, a result higher than that shown in the isograft group. Pharmacokinetic analyses of ¹²⁵I-labeled CXCL10 showed that distribution half-life was 0.34 hour and the elimination half-life was 9.83 hours. Dynamic whole body autoradiography images of ¹²⁵I-labeled CXCL10 showed excellent graft visualization in the allograft compared with the isograft group at all checking points, with visualization much more obvious at 12 and 24 hours.
These data suggest that CXCR3 is a promising imaging target for immune cell infiltration in early-stage acute rejection and ¹²⁵I-labeled CXCL10 can successfully image acute rejection with good pharmacokinetics.
已有报道称 CXCR3 与炎症细胞浸润有关。本研究旨在探讨 CXCR3 的配体碘-125 标记的 CXCL10 作为一种针对 CXCR3 的示踪剂，用于检测小鼠皮肤移植模型中的急性排斥反应。
以 BALB/c 和 C57BL/6 小鼠皮肤作为供体和 BALB/c 小鼠作为受体，建立同系和同种异体皮肤模型。我们使用逆转录-聚合酶链反应和免疫组织化学染色来检测 CXCR3 表达。采用碘代法制备 ¹²⁵I 标记的 CXCL10。在移植后第 8 天，通过尾静脉注射 ¹²⁵I 标记的 CXCL10 后，对同种异体/同系移植小鼠进行全身放射自显影和离体生物分布检查。
同种异体组织中 CXCR3 的表达高于同系对照组织。¹²⁵I 标记的 CXCL10 具有较高的特异性和亲和力。生物分布结果显示，同种异体组织中摄取的 ¹²⁵I 标记的 CXCL10 更高。24 小时时，靶与非靶比值为 3.01±0.25，高于同系移植组。¹²⁵I 标记的 CXCL10 的药代动力学分析显示，分布半衰期为 0.34 小时，消除半衰期为 9.83 小时。¹²⁵I 标记的 CXCL10 的动态全身放射自显影图像显示，与同系移植组相比，在所有检查点，同种异体移植中的移植物均能很好地可视化，在 12 和 24 小时时可视化更为明显。
这些数据表明，CXCR3 是早期急性排斥反应中免疫细胞浸润的有前途的成像靶点，¹²⁵I 标记的 CXCL10 可以成功地对急性排斥反应进行成像，具有良好的药代动力学特性。
