Myocardial uptake and biodistribution of newly designed technetium-labelled fatty acid analogues.
Nuclear medicine communications 2007 Aug 1; 28(8):637-645
Heintz A C, Jung C M, Stehr S N, Mirtschink P P, Walther M M, Pietzsch J J,
aDepartment of Anesthesiology cInstitute of Physiology dDepartment of Nuclear Medicine, Medical Facu
PURPOSE: In an effort to develop Tc-labelled fatty acids (FAs) for myocardial metabolism and flow imaging, several Tc analogues according to the '3+1' and the '4+1' mixed-ligand approach were synthesized and myocardial extraction was evaluated in non-working isolated guinea pig hearts. An example of biodistribution patterns in guinea pigs was determined by using one FA analogue. METHODS: The coordination moieties contain a +5, respectively +3, oxidation state metal core attached to the end position of a FA chain. FA complexes of the '3+1' and the '4+1' mixed-ligand type were prepared and investigated using the isolated heart model. To estimate the diagnostic value of the analogue Tc-FAs, the biodistribution of one well-extracted FA was evaluated. RESULTS: The '4+1' FA compounds achieved the highest uptake rates of all the technetium FAs investigated. In particular, the '4+1' Tc-C11-FA achieved at least a 2-fold higher ventricular extraction of the applied activity than the established control tracers including omega-(p-[I]iodophenyl)pentadecanoic FAs (BMIPP and IPPA) and Tc-MIBI. Furthermore, the '4+1' dodecanoic FA derivative and the thiadodecanoic FA derivative showed an extraction comparable to established I-labelled tracers. Biodistribution experiments performed for the thiadodecanoic FA derivative indicated a good heart/blood and heart/lung ratio and also a high uptake in the liver. In contrast, '3+1' Tc complexes showed a low myocardial extraction rate. Nevertheless, the differentiation in the extraction profile, which depends on the FA chain length and structure, indicates a specific heart uptake of these Tc-labelled FA derivatives as well. CONCLUSIONS: The excellent extraction rates found for '4+1' Tc-FAs indicate possibly promising structures for innovative myocardial tracers.