title: Labeling of fatty acid ligands with the strong electrophilic metal fragment [99mTc(N)(PNP)]2+ (PNP=diphosphane ligand).
abstract: The electrophilic metal fragment [(99m)Tc(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 pi-donor chelating systems to one terminus of the carbon chain to yield both dianionic and monoanionic bifunctional ligands (L). The resulting complexes, [(99m)Tc(N)(PNP)(L)] (0/+), exhibited the usual asymmetrical structure in which a Tc(triple bond)N group was surrounded by two different bidentate chelating ligands. Dianionic ligands gave rise to neutral complexes, while monoanionic ligands afforded monocationic species. Biodistribution studies were carried out in rats. An isolated perfused rat heart model was employed to assess how structural changes in the radiolabeled fatty acid compound affect the myocardial first pass extraction. Results showed that only monocationic complexes accumulated in myocardium to a significant extent. Conversely, neutral complexes were not efficiently retained 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 (99m)Tc-MIBI and (99m)Tc-DBODC with almost identical extraction values, a result that could be attributed to the presence of the monopositive charge. Instead, a slightly lower myocardial extraction 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 metabolic tracer [(123)I]IPPA revealed that the introduction of the metallic moiety partially hampers recognition of the labeled fatty acids by cardiac enzymes, and consequently, their behavior did not completely reflect myocardial metabolism.
authors.affiliation: Laboratory of Nuclear Medicine, Department of Radiological Sciences, University of Ferrara, 44100 Ferrara, Italy.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Cazzola
authors.forename: Elisa
authors.initials: E
authors.lastname: Benini
authors.forename: Micol
authors.initials: M
authors.lastname: Pasquali
authors.forename: Peter
authors.initials: P
authors.lastname: Mirtschink
authors.forename: Martin
authors.initials: M
authors.lastname: Walther
authors.forename: Hans-Jurgen
authors.initials: HJ
authors.lastname: Pietzsch
authors.forename: Licia
authors.initials: L
authors.lastname: Uccelli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Boschi
authors.forename: Cristina
authors.initials: C
authors.lastname: Bolzati
authors.forename: Adriano
authors.initials: A
authors.lastname: Duatti
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005227:Fatty Acids / Q000737:chemistry*; D005260:Female; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D015609:Organotechnetium Compounds / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013055:Spectrophotometry, Infrared
chemical_list: D005227:Fatty Acids; D008024:Ligands; D015609:Organotechnetium Compounds