Pilot Study of (64)CuCl₂ for PET Imaging of Inflammation.

Copper(II) ion (Cu(2+)) is the essential element for numerous pathophysiological processes in vivo. Copper transporter 1 (CTR1) is mainly responsible for maintaining Cu(2+) accumulation in cells, which has been found to be over-expressed in inflammatory tissues. Therefore, we explored the potential application of (64)CuCl₂ for PET imaging of inflammation through targeting CTR1. The animal models of H₂O₂ induced muscle inflammation and lipopolysaccaharide induced lung inflammation were successfully established, then imaged by small animal PET (PET/CT) post-injection of (64)CuCl₂, and PET images were quantitatively analyzed. H&E and immunohistochemical (IHC) staining and western blot experiments were performed for evaluating CTR1 levels in the inflammatory and control tissues. Both inflammatory muscle and lungs can be clearly imaged by PET. PET image quantitative analysis revealed that the inflammatory muscle and lungs showed significantly higher (64)Cu accumulation than the controls, respectively (p < 0.05). Furthermore, IHC staining and western blot analysis demonstrated that compared with the controls, CTR1 expression was increased in both the inflammatory muscle and lungs, which was consistent with the levels of (64)Cu(2+) accumulation in these tissues. (64)CuCl₂ can be used as a novel, simple, and highly promising PET tracer for CTR1 targeted imaging of inflammation.