PULMONARY ACCUMULATION OF NEUTRAL DIAMINE DITHIOL COMPLEXES OF TC-99M

Twenty-two neutral, lipid-soluble Tc-99m complexes have been synthesiz ed from diamine dithiol (DADT) ligands which vary in alkyl substitutio n pattern on nitrogen and carbon. The logarithm of the partition coeff icients (log PG), as well as the capacity factor k', of the purified c omplexes increased linearly with molecular weight. The biodistribution of these complexes was determined in normal mice, and several of the complexes selectively accumulated in the lungs as compared to the live r or other organs. Pulmonary accumulation varied greatly with subtle c hanges in structure, and a 30-fold range of lung uptake(1-31% of the i njected dose/organ) was observed for isomeric technetium complexes whi ch have identical molecular weights and similar log PC. Further, a par abolic relationship between lung uptake and log Pd was observed for a subset of the complexes which are derived from a homologous series of tetramethyl-DADT ligands. Neutral and lipophilic radiopharmaceuticals labeled with technetium can therefore be developed which exhibit struc turally specific uptake in the lung.