文摘
This report presents synthesis and evaluation of the 64Cu-labeled triphenylphosphonium (TPP) cations asnew radiotracers for imaging tumors by positron emission tomography. Biodistribution properties of 64Cu-L1, 64Cu-L2, 64Cu-L3, and 99mTc-Sestamibi were evaluated in athymic nude mice bearing U87MG humanglioma xenografts. The most striking difference is that 64Cu-L1, 64Cu-L2, and 64Cu-L3 have much lowerheart uptake (<0.6% ID/g) than 99mTc-Sestamibi (~18% ID/g) at >30 min p.i. Their tumor/heart ratiosincrease steadily from ~1 at 5 min p.i. to ~5 at 120 min p.i. The tumor/heart ratio of 64Cu-L3 is ~40 timesbetter than that of 99mTc-Sestamibi at 120 min postinjection. Results from in vitro assays show that 64Cu-L1is able to localize in tumor mitochondria. The tumor is clearly visualized in the tumor-bearing miceadministered with 64Cu-L1 as 30 min postinjection. The 64Cu-labeled TPP/TPA cations are very selectiveradiotracers that are able to provide the information of mitochondrial bioenergetic function in tumors bymonitoring mitochondrial potential in a noninvasive fashion.