Tc-99m labelled fatty acids for myocardial metabolism imaging


Tc-99m labelled fatty acids for myocardial metabolism imaging

Walther, M.; Pietzsch, H.-J.; Pietzsch, J.; Bergmann, R.; Wunderlich, G.; Mirtschink, P.; Deussen, A.

Ziel/Aim:

Radiolabelled fatty acids displaying efficient myocardial uptake and adequate retention are attractive candidates for the clinical evaluation of regional discrepancies in the cardiac metabolism and energy turnover (1). The aim of this work is the substitution of the accelerator produced radiolabel I-123 for FA against the low price generator radionuclide Tc-99m (2).

Methodik/Methods:

Synthesis and physico-chemical characterization of the new Tc-99m labelled FA derivatives were followed by in vitro and in vivo experiments for their biological evaluation. Experiments on isolated perfused rat hearts provide a simple and well reproducible approach to detect promising Tc-99m compounds for biodistribution experiments. Biodistribution and metabolism studies in male Wistar rats after a single intravenous injection of various Tc-99m-labelled FA were investigated (3).

Ergebnisse/Results:

A very rapid disappearance of Tc-99m tracer concentration from the blood circulation was observed for all compounds. C11S FA showed the highest uptake with 2.0% ID/g tissue (alternatively 3.6% by addition of Tween 80) in the rat heart. Liver and kidneys are mainly responsible for fast removal of Tc-99m derivatives from the circulation. At 5 min after injection, approximately 50% of the injected dose is liver-associated. A substantial fraction is cleared by the kidneys and approximately 6% of the injected dose is kidney-associated at 5 min p.i. Overall, fast systemic clearance of Tc-99m species after injection of Tc-99m labelled FA in the rat is explained by the rapid hepatobiliary and renal elimination of Tc-99m species. On the other hand, the low mean accumulation of Tc-99m compounds in the thyroid gland (<0.07 %ID at 5 min; <0.07 %ID at 60 min) and the stomach (<1.7 %ID at 5 min; < 3.9% at 60 min), respectively, which express the sodium-iodide transporter is indicative of a very low abundance of pertechnetate in vivo.

Schlussfolgerungen/Conclusions:

Experiments on isolated perfused rat hearts showed very high ventricular extraction rates of the FA complexes, being in the order C11 compound (26.6% ± 3.7, n= 12), C12 (24.4% ± 4.9, n= 5), and C11S (23.4% ± 4.9, n= 5). These extraction rates exceed considerably those achieved with the established iodinated FA [I-123]IPPA (15.5% ± 1.1).The metabolic in vivo studies reveal the complete ß-oxidation within one hour. Condition precedent for the use of the described Tc-FA in heart imaging are the improvement of the heart : liver ratio of 0.25±0.1 at 5 min p.i., which may be achieved by alterations of the FA binding mode to the “4+1” chelate unit and variations of the chelate position in the FA chain.

Literatur/References:

(1) Knapp, F. F. Jr., Kropp, J. (1995) Eur. J. Nucl. Med. 22(4), 361-381.
(2) Mach, R. H., Kung, H. F., Jungwiwattanaporn, (1991) Nucl. Med. Biol. 18, 215-226.
(3) M. Walther, C. M. Jung, R. Bergmann, (2006) Bioconjugate Chem. submitted

  • Lecture (Conference)
    45. Jahrestagung der Deutschen Gesellschaft für Nuklearmedizin, 25.-28.04.2007, Hannover, Deutschland
  • Abstract in refereed journal
    Nuklearmedizin 46(2007), A16
    ISSN: 0029-5566

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Publ.-Id: 9748