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 TctN 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.

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

E. Cazzola
Primo
;
M. Pasquali;UCCELLI, Licia;BOSCHI, Alessandra;DUATTI, Adriano
Ultimo
2008

Abstract

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 TctN 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.
2008
Cazzola, E.; Benini, E.; Pasquali, M.; Mirtschink, P.; Walther, M.; Pietzsch, H. J.; Uccelli, Licia; Boschi, Alessandra; Bolzati, C.; Duatti, Adriano...espandi
File in questo prodotto:
File Dimensione Formato  
fatty_acids.pdf

solo gestori archivio

Descrizione: Full text editoriale
Tipologia: Full text (versione editoriale)
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 722.29 kB
Formato Adobe PDF
722.29 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1653678
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 24
  • ???jsp.display-item.citation.isi??? 20
social impact