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Pyridinophane Ligands: An Attractive Chelator Platform for Mn-Based Imaging Agents
Tarek El Sayed1, Karna Terpstra1, Jennifer Whetter2
1Department of Chemistry, Beckman Institute for Advanced Science and Technology, The Neuroscience Program, Carle Illinois College of Medicine, University of Illinois at Urbana-Champaign, 600 S. Mathews Avenue, Urbana, Illinois 61801, United States.
None:
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.
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