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

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• 作者：Emiliano Cazzola ; Elisa Benini ; Micol Pasquali ; Peter Mirtschink ; Martin Walther ; Hans-Jurgen Pietzsch ; Licia Uccelli ; Alessandra Boschi ; Cristina Bolzati ; Adriano Duatti
• 刊名：Bioconjugate Chemistry
• 出版年：2008
• 出版时间：February 2008
• 年：2008
• 卷：19
• 期：2
• 页码：450 - 460
• 全文大小：721K
• 年卷期：v.19,no.2(February 2008)
• ISSN：1520-4812

文摘

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 ligands (L). The resulting complexes, [^99mTc(N)(PNP)(L)]^0/+, exhibited the usual asymmetrical structure in which a TcN 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 strucural 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 ^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 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 [¹²³I]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.