Noninvasive imaging of CCR2+ cells in ischemia-reperfusion injury after lung transplantation

Ischemia-reperfusion injury–mediated primary graft dysfunction substantially hampers short- and longterm 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. Both⁶⁴Cu-radiolabeled ECL1i peptide radiotracer (⁶⁴Cu-DOTA-ECL1i) and ECL1i-conjugated gold nanoclusters doped with⁶⁴Cu (⁶⁴CuAuNCs-ECL1i) showed specific detection of CCR2, which is upregulated during ischemiareperfusion injury after lung transplantation. Due to its fast pharmacokinetics,⁶⁴Cu-DOTA-ECL1i functioned efficiently for rapid and serial imaging of CCR2. The multivalent⁶⁴CuAuNCs-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.