title: Novel Preparation Methods of (52)Mn for ImmunoPET Imaging.
abstract: (52)Mn (t1/2 = 5.59 d, β(+) = 29.6%, Eβave = 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 (52)Mn in a state suitable for macromolecule labeling. To that end a (52)Mn production, purification, and labeling system is presented, and its applicability in preclinical, macromolecule PET is shown using the conjugate (52)Mn-DOTA-TRC105. (52)Mn is produced by 60 μA, 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 (52)Mn recovery, leading to a separation factor from Cr of (1.6 ± 1.0) × 10(6) (n = 4), and an average effective specific activity of 0.8 GBq/μmol (n = 4) in titration against DOTA. (52)Mn-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 (52)Mn biodistribution validates the in vivo PET data. Free (52)Mn(2+) (as chloride or acetate) is used as a control in additional mice to evaluate the nontargeted biodistribution in the tumor model.
authors: Stephen A
authors: SA
authors: Graves
authors: Reinier
authors: R
authors: Hernandez
authors: Technical University of Denmark , Center for Nuclear Technologies, 4000 Roskilde, Denmark.
authors: Jesper
authors: J
authors: Fonslet
authors: Christopher G
authors: CG
authors: England
authors: Hector F
authors: HF
authors: Valdovinos
authors: Paul A
authors: PA
authors: Ellison
authors: Todd E
authors: TE
authors: Barnhart
authors: Technical University of Denmark , Center for Nuclear Technologies, 4000 Roskilde, Denmark.
authors: Dennis R
authors: DR
authors: Elema
authors: TRACON Pharmaceuticals , San Diego, California 92122, United States.
authors: Charles P
authors: CP
authors: Theuer
authors: Weibo
authors: W
authors: Cai
authors: Robert J
authors: RJ
authors: Nickles
authors: Technical University of Denmark , Center for Nuclear Technologies, 4000 Roskilde, Denmark.
authors: Gregory W
authors: GW
authors: Severin
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D002857:Chromium / Q000737:chemistry; D005260:Female; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D007553:Isotope Labeling / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008345:Manganese / Q000737:chemistry* / Q000493:pharmacokinetics; D008807:Mice, Inbred BALB C; D049268:Positron-Emission Tomography / Q000379:methods*; D011854:Radiochemistry / Q000379:methods; D011868:Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D006573:Heterocyclic Compounds, 1-Ring; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D002857:Chromium; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D008345:Manganese; C579557:carotuximab