Preparation and in vivo characterization of (51)MnCl(2) as PET tracer of Ca(2+) channel-mediated transport

Manganese has long been employed as a T(1)-shortening agent in magnetic resonance imaging (MRI) applications, but these techniques are limited by the biotoxicity of bulk-manganese. Positron emission tomography (PET) offers superior contrast sensitivity compared with MRI, and recent preclinical PET studies employing (52g)Mn (t(1/2): 5.6 d, β(+): 29%) show promise for a variety of applications including cell tracking, neural tract tracing, immunoPET, and functional β-cell mass quantification. The half-life and confounding gamma emissions of (52g)Mn are prohibitive to clinical translation, but the short-lived (51)Mn (t(1/2): 46 min, β(+): 97%) represents a viable alternative. This work develops methods to produce (51)Mn on low-energy medical cyclotrons, characterizes the in vivo behavior of (51)MnCl(2) in mice, and performs preliminary human dosimetry predictions. (51)Mn was produced by proton irradiation of electrodeposited isotopically-enriched (54)Fe targets. Radiochemically isolated (51)MnCl(2) was intravenously administered to ICR mice which were scanned by dynamic and static PET, followed by ex vivo gamma counting. Rapid blood clearance was observed with stable uptake in the pancreas, kidneys, liver, heart, and salivary gland. Dosimetry calculations predict that 370 MBq of (51)Mn in an adult human male would yield an effective dose equivalent of approximately 13.5 mSv, roughly equivalent to a clinical [(18)F]-FDG procedure.