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Noninvasive Imaging of CCR 2 + Cells in Ischemia‐Reperfusion Injury After Lung Transplantation
Author(s) -
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.
Publication year - 2016
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.13907
Subject(s) - medicine , transplantation , ccr2 , lung transplantation , ischemia , reperfusion injury , lung , chemokine receptor , pathology , chemokine , immunology , immune system
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 (CCR 2) 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 CCR 2 binding peptide, ECL i1, that can be used to monitor inflammatory responses after organ transplantation. Both 64 Cu‐radiolabeled ECL 1i peptide radiotracer ( 64 Cu‐ DOTA ‐ ECL 1i) and ECL 1i‐conjugated gold nanoclusters doped with 64 Cu ( 64 CuAu NC s‐ ECL 1i) showed specific detection of CCR 2, which is upregulated during ischemia‐reperfusion injury after lung transplantation. Due to its fast pharmacokinetics, 64 Cu‐ DOTA ‐ ECL 1i functioned efficiently for rapid and serial imaging of CCR 2. The multivalent 64 CuAu NC s‐ ECL 1i with extended pharmacokinetics is favored for long‐term CCR 2 detection and potential targeted theranostics. This imaging may be applicable for diagnostic and therapeutic purposes for many immune‐mediated diseases.