64Cu-Labeled triphenylphosphonium and triphenylarsonium cations as highly tumor-selective imaging agents

This report presents synthesis and evaluation of the Cu-64-labeled triphenylphosphonium (TPP) cations as new radiotracers for imaging tumors by positron emission tomography. Biodistribution properties of (CU)-C-64-L1, Cu-64-L2, Cu-64-L3, and Tc-99m-Sestamibi were evaluated in athymic nude mice bearing U87MG human glioma xenografts. The most striking difference is that Cu-64-L1, Cu-64-L2, and Cu-64-L3 have much lower heart uptake (<0.6% ID/g) than Tc-99m-Sestamibi (similar to 18% ID/g) at >30 min p.i. Their tumor/heart ratios increase steadily from similar to 1 at 5 min p.i. to similar to 5 at 120 min p.i. The tumor/heart ratio of 64Cu-L3 is 40 times better than that of Tc-99m-Sestamibi at 120 min postinjection. Results from in vitro assays show that Cu-64-L1 is able to localize in tumor mitochondria. The tumor is clearly visualized in the tumor-bearing mice administered with Cu-64-L1 as 30 min postinjection. The Cu-64-labeled TPP/TPA cations are very selective radiotracers that are able to provide the information of mitochondrial bioenergetic function in tumors by monitoring mitochondrial potential in a noninvasive fashion.