Noninvasive Imaging of CCR2+ Cells in Ischemia‐Reperfusion Injury After Lung Transplantation. Issue 10 (14th July 2016)

• Record Type: Journal Article
• Authors: Liu, Y.; Li, W.; Luehmann, H. P.; Zhao, Y.; Detering, L.; Sultan, D. H.; Hsiao, H.‐M.; Krupnick, A. S.; Gelman, A. E.; Combadiere, C.; Gropler, R. J.; Brody, S. L.; Kreisel, D.
• Is Part Of: American journal of transplantation. Volume 16:Issue 10(2016:Oct.)
• Page Start: 3016
• Page End: 3023
• Publication Date: 2016-07-14
• Subjects: basic (laboratory) research/science -- lung transplantation/pulmonology -- ischemia reperfusion injury (IRI) -- diagnostic techniques and imaging: positron emission tomography; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.13907
• Languages: English
• ISSNs: 1600-6135

Abstract

Abstract : Ischemia‐reperfusion injury–mediated primary graft dysfunction substantially hampers short‐ and long‐term outcomes after lung transplantation. This condition continues to be diagnosed based on oxygen exchange parameters as well as radiological appearance, and therapeutic strategies are mostly supportive in nature. Identifying patients who may benefit from targeted therapy would therefore be highly desirable. Here, we show that C‐C chemokine receptor type 2 (CCR2) expression in murine lung transplant recipients promotes monocyte infiltration into pulmonary grafts and mediates graft dysfunction. We have developed new positron emission tomography imaging agents using a CCR2 binding peptide, ECLi1, that can be used to monitor inflammatory responses after organ transplantation. Both 64 Cu‐radiolabeled ECL1i peptide radiotracer ( 64 Cu‐DOTA‐ECL1i) and ECL1i‐conjugated gold nanoclusters doped with 64 Cu ( 64 CuAuNCs‐ECL1i) showed specific detection of CCR2, which is upregulated during ischemia‐reperfusion injury after lung transplantation. Due to its fast pharmacokinetics, 64 Cu‐DOTA‐ECL1i functioned efficiently for rapid and serial imaging of CCR2. The multivalent 64 CuAuNCs‐ECL1i with extended pharmacokinetics is favored for long‐term CCR2 detection and potential targeted theranostics. This imaging may be applicable for diagnostic and therapeutic purposes for many immune‐mediated diseases. Abstract : New positron emission tomography imaging agents, developed by the authors, use a CCR2 binding peptide that can monitor inflammatory responses noninvasively and serially after organ transplantation.