Development of small amphiphilic Rhenium and Tc-99m tricarbonyl complexes

Objectives Normal 0 Our aim was to develop a simple, small and non-specific “Technetium-based” complex with potential uptake in a large range of different tissues, by exploring the in-vivo properties of 3 novel, amphiphilic metal complexes of the [Tc(CO)₃]⁺ core.

Methods Three small, amphiphilic, C8, Tc-99m chelates were synthesized from the highly stable fac-[^99mTc(CO)₃(H₂O)₃]⁺ reagent. Tumor bearing mice were injected with the complexes and images obtained out to 4 hours on an animal SPECT/CT scanner. Biodistributions were also carried out at the 4 hour time point.

Results Normal 0 Labeling with [^99mTc(CO)₃]⁺ showed fast complex formation and high stability. We showed distinct localization of our small amphiphilic molecules in in vivo systems depending on the charge of their polar moiety obtained through biodistribution (4h) and imaging (15 minutes, 1h, 2h and 4h) with female C57Bl/6 mice.

Conclusions Normal 0 The obtained results show that where as a change of neutral charge to zwitterionic seems to facilitate metabolism of the corresponding compound through the intestinal system, the corresponding anionic compound is excreted at an even higher rate exclusively through the renal tract.Unfortunately, none of the 3 investigated complexes showed significant brain, tumor or heart uptake. The lack of heart uptake confirms negatively charged or zwitterionic complexes not to show suitable ionicity compared to other, cationic complexes with high myocaridial uptake.

Research Support We wish to thank the Natural Sciences and Engineering Research Council of Canada for generous financial support.