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

Twenty-two neutral, lipid-soluble Tc-99m complexes have been synthesized from diamine dithiol (DADT) ligands which vary in alkyl substitution pattern on nitrogen and carbon. The logarithm of the partition coefficients (log PG), as well as the capacity factor k', of the purified complexes 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 liver or other organs. Pulmonary accumulation varied greatly with subtle changes in structure, and a 30-fold range of lung uptake(1-31% of the injected dose/organ) was observed for isomeric technetium complexes which have identical molecular weights and similar log PC. Further, a parabolic 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 structurally specific uptake in the lung.