Novel Preparation Methods of 52Mn for ImmunoPET Imaging

Mn-52 (t(1/2) = 5.59 d, beta(+) = 29.6%, E-beta ave = 0.24 MeV) shows promise in positron emission tomography (PET) and in dual-modality manganese-enhanced magnetic resonance imaging (MEMRI) applications including neural tractography, stem cell tracking, and biological toxicity studies. The extension to bioconjugate application requires high-specific-activity Mn-52 in a state suitable for macromolecule labeling. To that end a Mn-52 production, purification, and labeling system is presented, and its applicability in preclinical, macromolecule PET is shown using the conjugate Mn-52-DOTA-TRC105. Mn-52 is produced by 60 mu A, 16 MeV proton irradiation of natural chromium metal pressed into a silver disc support. Radiochemical separation proceeds by strong anion exchange chromatography of the dissolved Cr target, employing a semiorganic mobile phase, 97:3 (v:v) ethanol:HCl (11 M, aqueous). The method is 62 +/- 14% efficient (n = 7) in Mn-52 recovery, leading to a separation factor from Cr of (1.6 +/- 1.0) X 10(6) (n = 4), and an average effective specific activity of 0.8 GBq/mu mol (n = 4) in titration against DOTA. Mn-52-DOTA-TRC105 conjugation and labeling demonstrate the potential for chelation applications. In vivo images acquired using PET/CT in mice bearing 4T1 xenograft tumors are presented. Peak tumor uptake is 18.7 +/- 2.7%ID/g at 24 h post injection and ex vivo Mn-52 biodistribution validates the in vivo PET data. Free Mn-52(2+) (as chloride or acetate) is used as a control in additional mice to evaluate the nontargeted biodistribution in the tumor model.