Pyridinophane Ligands: An Attractive Chelator Platform for Mn-Based Imaging Agents.

Manganese-based magnetic resonance imaging (MRI) contrast agents were developed using chelators derived from the 2,11-diaza[3.3](2,6)pyridinophane macrocycle to enhance Mn2+ relaxivity. The synthesized chelators were assessed to determine how coordination number and pendant arm selection affect the efficiency of the resulting Mn-based MRI contrast agents. Two compounds demonstrated significant potential: [Mn(TE-1)] exhibited relaxivity comparable to clinical gadolinium-based agents (3.6 mM-1 s-1 at 1.4 T), while [Mn(TE-4)] displayed rapid renal clearance and strong contrast enhancement in the kidney and bladder. In vivo PET imaging with 52Mn confirmed that [Mn(TE-4)] undergoes renal excretion, supporting its further development as an MRI or PET imaging agent. The lipophilic [Mn(TE-1)] exhibited both biliary and renal excretion, indicating its suitability as a blood pool MRI agent and for potential immuno-PET applications.