Date of Award
Doctor of Philosophy (PhD)
Manganese is an important element for biomedical research because of its roles as an essential micronutrient and as a neurotoxin from chronic elevated exposure, as well as the role of manganese(II) as a paramagnetic core for contrast agents in T1-weighted magnetic resonance imaging (MRI). Using a radiotracer of manganese provides excellent sensitivity for studying these phenomena, but only 52Mn met the criteria for our experiments: (1) a half-life (t1/2=5.6 days) that was long enough to examine timepoints over several days, (2) a half-life that was short enough to emit sufficient counts for a realistic scan time, and (3) emitted radiation of a variety and energy that were appropriate for existing pre-clinical imaging modalities. Manganese-52 is well-suited for imaging with positron emission tomography (PET) because it emits positrons with a low energy (E+=242 keV), which improves spatial resolution, and with an acceptable total abundance for positron emission (I+=29.6%) for adequate signal. Manganese-52 was produced on site by the 52Cr(p,n)52Mn reaction by bombarding non-enriched chromium (52Cr: 83.8%) with ~13 MeV protons that were accelerated in the CS-15 cyclotron at Washington University School of Medicine in St. Louis. Bombardments of stacks of thin chromium metal foils were used to measure nuclear cross-sections for the natCr(p,x)52,52m,54Mn reactions, with results that agreed closely to simulations and published results. Manganese-52 was separated chemically from bombarded chromium metal by cation- or anion-exchange chromatography. The separated product was used in experiments that included biodistribution by injection or inhalation, PET/CT or PET/MR in phantoms and rodents, and radiolabelling of a Mn(II)-based contrast agent for T1-weighted MRI. To reduce radiation dose to production personnel, we designed a remotely controlled, semi-automated module for the remote separation of 52Mn inside a lead hot cell. This module was similar to other modules that we designed, built, and tested for the routine, scaled-up production of larger quantities of the PET isotopes 89Zr and 86Y. We anticipate that the module for 52Mn will be completed, routine production of greater quantities of 52Mn will be achieved, and this radioisotope will continue to be used to study and image the interesting aspects and behaviors of manganese chemistry.
Suzanne Mark E. Lapi Anastasio
Parag Banerjee, Joseph P. Culver, Jason S. Lewis, Samuel A. Wickline,