Lei Jiang, MD, PhD

Purpose: Copper(II) ion (Cu2+) is an essential trace nutrient required for numerous biological processes and abnormalities including inflammation in living subjects. Copper transporter 1 (CTR1) is mainly responsible for maintaining Cu2+ accumulation in cells, which has been found to be over-expressed in inflammatory tissues. Therefore, we investigated the potential application of 64CuCl2 PET for inflammation imaging through targeting of CTR1. Methods: The animal models of H2O2 induced muscle inflammation and lipopolysaccaharide (LPS) induced lung inflammation were successfully established. Both models (n=4 per group) were then imaged by small animal PET (PET/CT) after injection of 64CuCl2, 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 muscle and lungs. Results: Both inflammatory muscle and lungs can be clearly imaged by PET(Figure 1A and 2A). Further PET image quantitative analysis revealed that the inflammatory muscle showed significantly higher 64Cu accumulation than the control (P < 0.05) (Figure 1B and 1C). Similarly, compared with the control lungs, the inflammatory lungs displayed increased 64Cu uptake (P < 0.05) (Figure 2B and 2C). Furthermore, IHC staining and western blot analysis demonstrated that compared with the controls, the elevated expression of CTR1 was observed in both the inflammatory muscle and lungs, which was consistent with the levels of 64Cu2+ accumulation in these tissues. Conclusions: 64CuCl2 can be used as a novel, simple and highly promising PET probe for CTR1 targeted imaging of inflammation.