“Click” chemistry toward bis(DOTA-derived) heterometallic complexes: potential bimodal MRI/PET(SPECT) molecular imaging probes

Abstract

A general synthetic methodology has been developed for the preparation of DOTA-derived heterometallic omplexes as potential bimodal MRI/PET(SPECT) molecular probes. Both alkyne- and azide substituted DOTA-derived chelators have been synthesized and metallated with Gd³⁺ (MRI reporter) or “cold” isotopes of Cu²⁺, Ga³⁺ and In³⁺ (potential PET or SPECT reporters). The Cu⁺-catalyzed Huisgen [3 + 2] cycloaddition has been utilized as a key step in the synthesis of potential bimodal MRI/PET(SPECT) molecular probes. A preliminary optimization of the reaction conditions has been carried out to make the reaction conditions compatible with the radioactive isotopes of Cu²⁺, Ga³⁺ and In³⁺ possessing short life times. The MRI sensitivity of the potential bimodal MRI/PET(SPECT) molecular probes has been determined and compared to that associated with a clinically used MRI contrast agent.