Synthesis, characterization and biodistribution of new fatty acids conjugates bearing N,N,N-donors incorporated [99mTc/Re(CO)3]+

Abstract

[^99mTc(CO)₃]⁺-6-[N-(2-dipicolyl)amino]hexanoic acid (1a) and [^99mTc(CO)₃]⁺-11-[N-(2-dipicolyl)amino]undecanoic acid (1b) were prepared by incorporating [^99mTc-(CO)₃]⁺ into 6-[N-(2-dipicolyl)amino]hexanoic acid and 11-[N-(2-dipicolyl)amino]undecanoic acid, respectively. The overall radiochemical yield of 1a and 1b was from 79.7% to 91.3% and radiochemical purity after HPLC purification was more than 94%. The resulting complexes were found to be chemically stable when incubated in SD rat serum for 3 h at 37 °C. Tissue distribution studies in normal mice showed that high initial uptake of Tc-99m complexes were observed, followed by slow clearance from the heart. The maximum heart-to-blood ratio of 1a was 1.46 at 60 min, but 1b showed a poor heart-to-blood ratio. By estimating the tissue distribution and the computing result of the molar volume and the solvation free energy of Tc-99m chelating groups, a small-size and monocationic Tc-99m core is very important to enhance the myocardial accumulation and low liver uptake for the fatty acid tracers.