Synthesis and biological evaluation of a new type of technetium-labelled fatty acids for myocardial metabolism imaging

Introduction: In an effort to develop technetium-labelled fatty acid analogues for myocardial metabolism imaging rhenium model complexes and their ^99mTc analogues were synthesized according to the '4+1' mixed-ligand approach and investigated in vitro and in vivo.

Materials and Methods: The rhenium model complexes were completely characterised by NMR, IR, MS, EA and the geometrical impact of the chelate unit on the integrity of the fatty acid head structure was determined by single crystal X-ray analyses. To estimate the diagnostic value of the ^99mTc-labelled fatty acids the compounds were investigated using the isolated constant-flow-perfused guinea pig heart model (see presentation A. Heintz et al.), in cell-uptake experiments and in biodistribution studies using male Wistar rats (5 - 6 weeks old, body weight 151 ± 15 g).

Results: The new fatty acid tracers contain the metal core in the oxidation states +3, well-wrapped in a trigonal-bipyramidal coordination moiety which is attached at the omega-position of a fatty acid chain. This structural feature is considered to be a good imitate of the well-established iodinated phenyl fatty acid. The formation of the rhenium models was accomplished by ligand exchange reactions using different pre-formed rhenium precursors. Noticable heart uptake of the ^99mTc tracers being in the order of 2 % ID/g 5´p.i. and accompanied by a good heart to blood ratio of 8.6 confirms the remarkably results of the perfused heart experiments. A significant time-dependent cell uptake in HepG2 cells is shown for two representatives.

Conclusion: Further species such as mice and guinea pigs will be involved to characterise in vivo patterns of those derivatives, that show high extraction rates in the isolated constant-flow-perfused guinea pig heart model. While the tracers are superior to other described Tc-fatty acid imitates with regard to good heart to blood ratios, heart to liver ratio has to be improved. For this, chemical modifications will be performed at the chelating part as well as at the alkyl chain.