Abstract
In this study, synthesis, radiochemical characteristic, tumor cell uptake, and biodistribution of 67Ga and 68Ga l led 1,4,7,10-tetra- azacyclododecane N,N’,N”,N’”-tetraacetic acid-Glutamine（DOTA-Gln）were investigated. First, the DOTA-Gln couple was prepared by two different synthetic methods, in liquid phase (traditional) and in solid phase. Subsequently, both 68Ga and 67Ga were l led to this couple to get the radiol led conjugate. L ling efficiency, lipophilicity, and stability of 68Ga-DOTA-Gln and 67Ga-DOTA-Gln were surveyed by the radioanalytical methods including thin layer chromatography and electrophoresis. Finally, animal biodistribution study, cell survival test, toxicity test, and cell uptake trials were undertaken to assess the potential of the 68Ga-DOTA-Gln as a PET imaging agent.For labeling, 68Ga-DOTA-Gln and 67Ga-DOTA-Gln were acquired by ligand-ligand exchange of DOTA-Gln with 68Ga (acac)3 or 67Ga-citrate; the reaction was facilitated via supersonication at room temperature for 20 min. Labeling efficiency of either 68Ga or 67Ga labeled DOTA-Gln could reach ca. 90%. From radiochemical analysis including TLC and electrophoresis, the radiolabeled conjugate was evidenced to be anionic and hydrophilic. The stability of 67Ga-DOTA-Gln was found to be high even storage for 72h. In cell uptake experiment, 67Ga-DOTA-Gln showed negligible chemical toxicity and radiation damage for spontaneous and non-immunogenic fibrosarcoma cells (Nfsa). The cell uptake increased with increasing cell numbers and elongating the elapsed time. From the results, it is indicated that 68Ga-DOTA-Gln has the potential as a PET imaging agent for diagnosing tumors.In the biodistribution study, 67Ga-DOTA-Gln was found to excrete mainly via kidney and urinary tract. Tumor uptake increased with the elapsed time, reaching a maximum at 8.54% (% ID/g organ) at 1h postinjection. The uptake ratio of tumor to muscle was ca. 1.3, suggesting that 67Ga-DOTA-Gln possesses the potential as a diagnostic agent for tumors. In addition, the high uptake and retention of 67Ga-DOTA-Gln in the spleen may reveal another purpose pertaining to nuclear medicine.