Copper-labeled rhodamine derivatives for cancer imaging

The enhanced mitochondrial potential in carcinoma cells is an important characteristic of cancer. It is of great current interest to develop a radiotracer that is sensitive to the mitochondrial potential changes at the early stage of tumor growth. In this thesis, we designed and synthesized four novel 64Cu-labeled DOTA-K-Rd derivatives with different substitutes of hydroxyl group, aminoethyl group, aminomethyl group and azaheterocyclic structure on Rodamine targeting moieties. Four radiotracers were evaluated on athymic nude mice bearing U87MG human glioma xenografts. All of the four radiotracers had higher glioma uptake than that of 64Cu(DO3A-xy-TPEP) over the 1 h period, which was reported to have higher tumor selectivity and uptake than those of Tc-99m-Sestamibi. 64Cu(DOTA-K-FAM) showed the highest tumor uptake, and lowest blood and muscle uptakes among the 4 Rodamine derivative radiotracers. Its tumor/kidney, tumor/lung and tumor/liver ratios were better than the other 3 radiotracers and comparable to those of 64Cu(DO3A-xy-TPEP). The results of cellular staining study showed that Cu(DOTA-K-FAM) was able to localize in mitochondria due to the enhanced negative mitochondrial potential in U87MG glioma cells. On the basis of the results from this thesis, it was concluded that 64Cu(DOTA-K-FAM) represents a new class of promising PET radiotracers for noninvasive glioma imaging. In addition, the effects of polar group, bulky group and expansion of the ring planarity of Rodamine targeting moiety on tumor uptake were also summarized in this thesis