Synthesis and biologic evaluation of monocationic asymmetric 99mTc-nitride heterocomplexes showing high heart uptake and improved imaging properties (Articolo in rivista)

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  • Synthesis and biologic evaluation of monocationic asymmetric 99mTc-nitride heterocomplexes showing high heart uptake and improved imaging properties (Articolo in rivista) (literal)
Anno
  • 2003-01-01T00:00:00+01:00 (literal)
Alternative label
  • Boschi A.; Uccelli L.; Bolzati C.; Duatti A.; Sabba N.; Moretti E., Di Domenico G.; Zavattini G.; Refosco F.; Giganti M. (2003)
    Synthesis and biologic evaluation of monocationic asymmetric 99mTc-nitride heterocomplexes showing high heart uptake and improved imaging properties
    in The Journal of nuclear medicine (1978. Online)
    (literal)
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  • Boschi A.; Uccelli L.; Bolzati C.; Duatti A.; Sabba N.; Moretti E., Di Domenico G.; Zavattini G.; Refosco F.; Giganti M. (literal)
Pagina inizio
  • 806 (literal)
Pagina fine
  • 814 (literal)
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  • http://jnm.snmjournals.org/content/44/5/806.full.pdf+html (literal)
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  • 44 (literal)
Rivista
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  • Trattasi di una classe di nuovi potenziali radiofarmaci di perfusione cardiaca a base di Tc-99m. La molecola, di concezione innovativa, è costituita da un gruppo metallo-nitruro sul quale sono legati una difosfina e un ditiocarbammato. Il mixing di atomi donatori assicura una stabilità elevata del sistema anche nei fluidi biologici. Variando i sostituenti alla difosfina e al ditiocarbammato si possono migliorare le proprietà biologiche in termini di % di captazione del prodotto sul cuore di animali modello (ratti). Inoltre risulta elevata la clearance da organi quali fegato e polmoni. Il tutto ha un effetto migliorativo sulla qualità della captazione a livello del miocardio (literal)
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  • Scopu (literal)
  • ISI Web of Science (WOS) (literal)
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  • 1,2,4-6,10 Laboratory of Nuclear Medicine, Dept. of Clin. and Exp. Medicine, University of Ferrara, Ferrara, Italy 7,8 Department of Physics, University of Ferrara, Ferrara, Italy 3,9 Ist. Chim. Inorg. e Delle Superfici, Consiglio Nationale Delle Ricerche, Padua, Italy 4 Laboratory of Nuclear Medicine, Dept. of Clin. and Exp. Medicine, University of Ferrara, Via L. Borsan 46, 44100 Ferrara, Italy (literal)
Titolo
  • Synthesis and biologic evaluation of monocationic asymmetric 99mTc-nitride heterocomplexes showing high heart uptake and improved imaging properties (literal)
Abstract
  • The preparation, characterization and first biological evaluation in rats of a novel class of monocationic Tc-99m heart imaging agents are reported. The complexes are represented by the general formula [99mTc(N)(PNP)(L)]+, where L is the monoan-ionic form of a dithiocarbamate ligand of the type [R1(R2)-N-C(=S)S]-, and PNP is a diphosphine ligand of the type [(R3)2P-(CH2)2]2-N(R4) (R1-4 = organic functional groups). Methods: The new complexes were prepared using both liquid and freeze-dried formulations through a 2-step procedure. The first step involved the formation of the [TcßN]2+ group through the reaction of [99mTcO4]- with succinic dihydrazide (SDH) as a donor of nitride nitrogen atoms (N3-) in the presence of Sn2+ ions. This was followed by the simultaneous addition to the reaction solution of the ligand PNP and of the sodium salt of the dithiocarbamate ligand (NaL) to afford the final prod-ucts [99mTc(N)(PNP)(L)]+. The chemical identity of the resulting Tc-99m complexes was determined by comparing their chromatographic properties with those of the cor-responding 99gTc analogs prepared using the long-lived isotope Tc-99g and charac-terized by spectroscopic and crystallographic techniques. Ex-vivo biodistribution studies were conducted in rats. In-vivo tomographic images of rat.s heart were ob-tained using a small-animal SPET scanner Results: The complexes [99mTc(N)(PNP)(L)]+ are monocationic and possess a distorted square-pyramidal ge- ometry where the TcßN multiple bound occupies an apical position and the di-phosphine and dithiocarbamate ligands span the residual four coordination positions on the basal plane through the two phosphorus atoms and the two sulfur atoms, re-spectively. Imaging and biodistribution studies demonstrated that these radiopharma- ceuticals localize selectively into the myocardium of rats, and are retained in this re-gion for a prolonged time. Kinetics of heart uptake and clearance were found to be influenced by the variation of the lateral R1-4 groups. Blood and lung washouts were extremely fast. Elimination occurred mostly through the kidneys and the liver. Sur-prisingly, after one hour from injection, liver activity was almost negligible. Analysis of heart/liver and heart/lung uptake ratios showed that these values increase exponen-tially in time, and become much higher than those determined for 99mTc-Sestamibi and 99mTc-Tetrofosmin. These findings were confirmed by analysis of high-quality SPET images collected in rats for the new complexes and compared with images ob-tained with 99mTc-Sestamibi and 99mTc-Tetrofosmin. Conclusion: The high myocar-dial uptake combined with the very high value of heart/lung and heart/liver ratios indicate that the complexes [99mTc(N)(PNP)(L)]+ exhibit very favorable distribution properties and could be potentially used to obtain SPET cardiac images with improved quality. (literal)
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