Mercaptoimidazole Derivatives Labelled with ¹¹C/^99mTc for the Targeting of 5-HT_1A Receptors

Our research group has focused on mercaptoimidazole derivatives as the lead structure to design radioactive probes for in vivo imaging of 5-HT_1A receptors. This type of compounds can be labelled directly with ¹¹C or can be used to prepare tripodal ligands suitable to stabilize the fac-[M(CO)₃]⁺ (M = Re, ^99mTc) moieties.^1,2 Interestingly, this versatility allows an easy assessment of the influence of the bulkier metallic fragment on the biological properties of PET (¹¹C) or SPECT (^99mTc) radioligands bearing a common pharmacophore.
Scheme 1
In this communication, we report on the radiosynthesis, characterization and biological evaluation of mercaptoimidazole piperazinyl derivatives labelled with ¹¹C (1) and with ^99mTc (2 and 3) (Scheme 1). It will be discussed their interest as radioactive probes for imaging 5-HT_1A receptors by means of PET or SPECT, as well as the effect of the presence of the organometallic moiety on the affinity and biodistribution profile of the compounds.
Acknowledgments: R. Garcia and L. Maria thank FCT for PhD and Post-Doc grants, respectively. This work has been partially supported by the FCT (POCTI/2001/QUI/42939).
[1] Garcia, R; Xavier, C.; Paulo, A.; Santos, I.; Kniess, T.; Bergmann, R.; Wüst, F. J. Labelled Cpd. Radiopharm. 2005, 48, 301.
[2] Garcia, R.; Paulo, A.; Domingos, A.; Santos, I.; Ortner, K.; Alberto, R. J.Am Chem. Soc. 2000, 122, 11240.