All ETDs from UAB

Advisory Committee Chair

Suzanne E Lapi

Advisory Committee Members

Eugenia Kharlampieva

Benjamin M Larimer

Anna G Sorace

Gayan B Wijeratne

Document Type

Dissertation

Date of Award

2023

Degree Name by School

Doctor of Philosophy (PhD) College of Arts and Sciences

Abstract

Manganese (Mn) has the potential to be an important element in biomedical research as different isotopes of Mn have the characteristics to be used for both positron emission tomography (PET) and magnetic resonance imaging (MRI). Manganese(II) (55Mn) is paramagnetic which makes it useful as a contrast agent in T1-weighted magnetic resonance imaging (MRI). Mn as a radiotracer provides excellent sensitivity for studying 55Mn, but only Manganese-52 (52Mn) met the criteria for this research. 52Mn has a half-life (t1/2 = 5.591 days) that was long enough to optimize purification, chemistry and examine timepoints over several days. 52Mn decays by positron emission 29.4% with an average positron energy of 242 keV which is well-suited for imaging with PET. 52Mn was produced via the nuclear reaction nat/52Cr(p,n)52Mn using natural Cr targets on a TR24 cyclotron. Multiple Cr targets were made and tested for 52Mn production including natural Cr foils, natural Cr metal powder pellets, chromium-52 oxide (52Cr2O3), and electroplated Cr(III) targets. Targets were irradiated at 12.5 MeV incident on the Cr target material. To reduce radiation dose to production personnel, a remotely controlled semi-automated system was designed for the purification of 52Mn inside a shielding cell. 52Mn separation was carried out on AG1-X8 anion exchange resin utilizing the semi-automated system. Cr was flushed from the columns with a series of acid washes followed by elution of the final 52Mn product in 0.1 M or 6 M hydrochloric acid (HCl). The purified 52Mn was then characterized with gamma spectroscopy, used for further radiochemistry and scanned by PET/CT or PET/MRI in phantoms. PET/MRI and PET/CT phantoms were prepared with 52Mn radioactivity ranging from 0-20 μCi and 55Mn concentrations ranging from 0-1 mM. The 52Mn/55Mn solution was used for PET/MRI and PET/CT scans where PET was acquired for 10 min and MRI was collected at various inversion times ranging from 200-2100 ms to create a T1 map. Natural Cr has 4 stable isotopes with the 52Cr abundance at 83.8% which makes this a viable alternative until a recycling method for 52Cr targets is established. 52Mn was purified from natural Cr foils using 5 x 0.5 cm, gravity fed columns that yielded non-decay corrected recoveries of 70.8 ± 3.3% with a time of 8.2 ± 0.6 h whereas 52Mn from natural Cr pressed powder pellets and electroplated Cr targets purified using pressurized 1 mL SPE tubes yielded non-decay corrected recoveries of 94.5 ± 2.4 % with a time of 4.2 ± 0.4 h. Phantom images showed promising results with 52Mn/55Mn combination where the varying amounts of radioactivity vs. Mn concentration was clearly observed. The amounts of radioactivity added to each phantom vial aligned well with the regions of interest (ROIs) drawn on each phantom utilizing the MIM image analysis software which led us to move forward with in vivo studies. The [52Mn]MnCl2 phantoms contained activities ranging from 0-20 μCi of 52Mn as assessed with a high purity germanium detector and activities collected from the ROIs on the PET image which exhibited a linear agreement. The T1 relaxivity of the phantoms was calculated to be 7.4 mM*s-1 (R2=0.9943). These results demonstrated a robust method for the cyclotron production of 52Mn via proton induced reactions that could be used with either natural or enriched Cr targets. The semi-automated system that was designed, developed and tested improved 52Mn purification yields, purification times and reduced the dose to personnel by operating it via remote control outside of a shielding cell. Preliminary phantom studies show promising results for the combination of 52Mn/55Mn as a PET/MRI imaging agent. The strategies developed in this work and data from initial studies will be used to support future work for optimization of the enriched Cr target, automated purification system and to compare the in vitro and in vivo efficacy of 52Mn/55Mn in PET/MRI studies.

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