Development of Ca2+ Responsive Contrast Agents for fMRI

Magnetic resonance imaging (MRI) using contrast agents has been widely employed in diagnostic imaging and biomedical research. For this purpose, Gd3+ based complexes are commonly utilized. Recently, responsive (smart) contrast agents (SCAs) are being developed in order to aid better understanding of biological processes [1] They are able to report physiological or pathophysiological changes by altering the MR signal they produce. However the routine in vivo use of SCA is hampered due to challenges such as lack of tools to localize or quantify the agents, low MR signal, non-specific delivery etc. To overcome these challenges, one of the meaningful strategies is to conjugate SCA to various functional molecules such as dendrimers, nanoparticles, delivery vectors or fluorescent tags. The essential requirement when coupling SCAs to functional molecules is retaining their crucial physico-chemical properties in terms of MRI activity. Hence, the overall objective of our approach was to develop synthetic strategies in which modified DO3A chelator is appended with different linkers for further functionalization. Diverse synthetic strategies were successfully developed using liquid, as well as solid phase chemistry [2]. The SCA were modified and they still robustly response to Ca2+. The newly developed strategies open pathways to improve in vivo applicability of DO3A-based SCAs and to serve as better in vivo reporters in future fMRI experiments