Synthesis and biodistribution of 99mTc-peptides conjugated adenine as tumor imaging agents

99mTc-labeled peptides have become an important class of tumor imaging agents and have been given more attention. But their tumor uptake and the uptake ratio of tumor to normal tissue need to be improved. Tumor cells have prosperous nucleic acid synthesis and the bases can be accumulated in tumor proliferative cells. In the present study, two peptides conjugated adenine are synthesized and labeled with 99mTc. The complexes are evaluated as tumor imaging agents. A dipeptide (N-(tritylmercaptoacetyl) glycyl glycine, Tr-MAG2) and a tripeptide (N-(tritylmercaptoacetyl) diglycyl glycine, Tr-MAG3) are conjugated with adenine. Two new ligands containing adenine are characterized by IR, NMR, MS and elemental analysis. Two peptide ligands containing adenine, [N-(mercaptoacetyl diglycyl amino ethyl) adenine, MAG2-Ade] and [N-(mercaptoacetyl triglycyl amino ethyl)adenine, MAG3-Ade], are labeled with 99mTc using the solution of SnCl2 as reducing agent. The labeled compounds are injected into the mice bearing S180 tumor via the tail vein. Scintigraphy is performed with GE MPR SPECT at 1h, 2 h, 3 h and 5 h postinjection, respectively. Biodistributions are measured at 3 h postinjection and the percentage of injected dose per gram tissue (ID%/g ) and the uptake ratios of tumor to normal tissue (T/NT) are calculated. For 99mTc-MAG2-adenine and 99mTc-MAG3-adenine, the uptake radios of tumor to muscle at 3 h postinjection are 5.70 and 4.92, respectively. Scintigraphic imagings show that the labeled compounds can be accumulated in tumor after 1h postinjection and have a good contrast of tumor to surrounding tissue after 3 h postinjection. But the high radioactivity uptake of two complexes in abdomen are also found. The biodistribution and scintigraphic imaging study show that the specific localization of 99mTc-MAG2-adenine and 99mTc-MAG3-adenine in tumor are observed and the high contrasted tumor images can be obtained, which suggest their potential utility as tumor imaging agents But the high radioactivity of abdomen could prevent the tumor imaging in this area.