Uptake and retention of manganese contrast agents for PET and MRI in the rodent brain

Abstract

Manganese-enhanced magnetic resonance imaging (MRI) is an established neuroimaging method for signal enhancement, tract tracing, and functional studies in rodents. Along with the increasing availability of combined positron emission tomography (PET) and MRI scanners, the recent development of the positron-emitting isotope 52Mn has prompted interest in the use of Mn2+ as a dual-modality contrast agent. In this work, we characterized and compared the uptake of systemically delivered Mn2+ and radioactive 52Mn2+ in the rat brain for MRI and PET, respectively. Additionally, we examined the biodistribution of two formulations of 52Mn2+ in the rat. In MRI, maximum uptake was observed one day following delivery of the highest MnCl2 dose tested (60 mg/kg), with some brain regions showing delayed maximum enhancement 2–4 days following delivery. In PET, we observed low brain uptake after systemic delivery, with a maximum of approximately 0.2% ID/g. We also studied the effect of final formulation vehicle (saline compared with MnCl2) on 52Mn2+ organ biodistribution and brain uptake. We observed that the addition of bulk Mn2+ carrier to 52Mn2+ in solution resulted in significantly reduced 52Mn2+ uptake in the majority of organs, including the brain. These results lay the groundwork for further development of 52Mn PET or dual Mn-enhanced PET–MR neuroimaging in rodents, and indicate several interesting potential applications of 52Mn PET in other organs and systems. Copyright © 2016 John Wiley & Sons, Ltd.