Labeling of Fatty Acid Ligands with the Strong Electrophilic Metal Fragment [^99mTc(N)(PNP)]²⁺ (PNP = Diphosphane Ligand)

The electrophilic metal fragment [^99mTc(N)(PNP)]²⁺ (PNP = diphosphane ligand) has been employed for the labeling of fatty acid chains of different lengths. To provide a site-specific group for the attachment of the metallic moiety, the fatty acid derivatives were functionalized by appending a bis-mercapto or, alternatively, a dithiocarbamato π-donor chelating systems to one terminus of the carbon chain to yield both dianionic and monoanionic bifunctional li-gands (L). The resulting complexes, [^99mTc(N)(PNP)(L)]^0/+, exhibited the usual asymmetrical structure in which a Tc≡N group was surrounded by two different bidentate chelating ligands. Dianionic ligands gave rise to neutral complexes, while monoanionic ligands afforded mono-cationic species. Biodistribution studies were carried out in rats. An isolated perfused rat heart model was employed to assess whether the new labeled fatty acids still were recognized as substrates for β-oxidation. Results showed that only monocationic complexes accumulated in myocardium to a significant extent. Conversely, neutral complexes were not efficiently re-tained into the heart region and rapidly washed out. In isolated perfused rat heart experiments, monocationic complexes exhibited a behavior similar to that of the monocationic flow tracers ^99mTc-MIBI and ^99mTc-DBODC with almost identical extraction values, a result that could be attributed to the presence of the monopositive charge. Instead, a slightly lower myocardial ex-traction was found for neutral complexes. Comparison of the observed kinetic behavior of neutral complexes in the isolated perfused rat heart model with that of the myocardial meta-bolic tracer [¹²³I]IPPA revealed that the introduction of the metallic moiety partially hamper recognition of the labeled fatty acids by cardiac enzymes and, consequently, their behavior did not completely reflect myocardial metabolism.