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Integrating MRI and Chemokine Receptor CXCR4-Targeted PET for Detection of Leukocyte Infiltration in Complicated Urinary Tract Infections After Kidney Transplantation
The Journal of Nuclear Medicine ( IF 9.1 ) Pub Date : 2017-11-01 , DOI: 10.2967/jnumed.117.193037
Thorsten Derlin , Faikah Gueler , Jan Hinrich Bräsen , Jessica Schmitz , Dagmar Hartung , Thomas R. Herrmann , Tobias L. Ross , Frank Wacker , Hans-Jürgen Wester , Marcus Hiss , Hermann Haller , Frank M. Bengel , Katja Hueper

Complicated urinary tract infections (UTIs) are frequent in immunosuppressed patients after kidney transplantation and may lead to allograft failure or urosepsis. Noninvasive detection of allograft involvement as well as localization of the primary site of infection are challenging. Therefore, we sought to determine whether molecularly targeted PET, combined with diffusion-weighted MRI, enables detection of leukocytes in renal allografts. Methods: Thirteen kidney transplant recipients with complicated UTIs underwent both PET with a specific CXCR4 ligand, 68Ga-pentixafor, and diffusion-weighted MRI. The spatial distribution and intensity of CXCR4 upregulation in renal allografts as determined by SUVs on PET and diffusion restriction as determined by apparent diffusion coefficients (ADCs) on MRI were analyzed and compared with urinalysis, clinical chemistry and bacteriology, and biopsy, if available. Results: Combined PET/MRI detected acute allograft infection in 9 patients and lower UTI/nonurologic infections in the remaining 4 patients. Leukocyte infiltration was identified by areas of CXCR4 upregulation compared with unaffected parenchyma in PET (SUVmean, 4.6 vs. 3.7; P < 0.01), corresponding to areas with increased cell density in MRI (ADCmin, 0.89 vs. 1.59 × 10−3 mm2/s, P < 0.01). Allograft CXCR4 signal was paralleled by CXCR4 upregulation in lymphoid organs. Histopathologic evaluation supported a correlation between CXCR4 signal and presence of leukocytes. Conclusion: Combined CXCR4-targeted PET/MRI with 68Ga-pentixafor may enable the noninvasive detection of leukocytes in renal allografts. This novel methodology may refine the characterization of infectious and inflammatory kidney diseases and may serve as a platform for future clinical studies targeting allograft infection.



中文翻译:

整合MRI和趋化因子受体CXCR4靶向PET检测肾脏移植术后复杂尿路感染中的白细胞浸润

肾脏移植后,免疫抑制患者经常出现复杂的尿路感染(UTI),并可能导致同种异体移植失败或尿毒症。无创检测同种异体移植受累以及感染的主要部位的定位是具有挑战性的。因此,我们试图确定分子靶向的PET与扩散加权MRI结合是否能够检测肾同种异体移植物中的白细胞。方法: 13位复杂的UTI的肾移植受者均接受了具有特定CXCR4配体的PET,68Ga-pentixafor和扩散加权MRI。分析了SUV在PET上通过SUV确定的肾移植物中CXCR4上调的空间分布和强度,以及在MRI上通过表观扩散系数(ADC)确定的扩散限制在CXCR4上调的空间分布和强度,并与尿液分析,临床化学和细菌学以及活检(如果有的话)进行了比较。结果: PET / MRI组合检测出9例患者接受了急性同种异体移植物感染,其余4例检测到了较低的UTI /非泌尿外科感染。与未受影响的实质相比,PET中CXCR4上调的区域确定了白细胞浸润(SUV平均值,4.6 vs. 3.7;P <0.01),与MRI中细胞密度增加的区域相对应(ADC min,0.89 vs. 1.59×10 -3)。毫米2 / S,P <0.01)。同种异体移植CXCR4信号与淋巴器官中的CXCR4上调平行。组织病理学评估支持CXCR4信号与白细胞存在之间的相关性。结论:将靶向CXCR4的PET / MRI与68 Ga-pentixafor联合使用可实现无创检测肾脏同种异体移植物中的白细胞。这种新颖的方法可以改善感染性和炎症性肾脏疾病的特征,并可以作为针对同种异体移植感染的未来临床研究的平台。

更新日期:2017-11-01
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