Journal article
Novel Preparation Methods of Mn-52 for ImmunoPET Imaging
Bioconjugate chemistry, Vol.26(10), pp.2118-2124
10/01/2015
DOI: 10.1021/acs.bioconjchem.5b00414
PMCID: PMC4618027
PMID: 26317429
Abstract
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.
Details
- Title: Subtitle
- Novel Preparation Methods of Mn-52 for ImmunoPET Imaging
- Creators
- Stephen A. Graves - University of Wisconsin–MadisonReinier Hemandez - University of Wisconsin–MadisonJesper Fonslet - Technical University of DenmarkChristopher G. England - University of Wisconsin–MadisonHector F. Valdovinos - University of Wisconsin–MadisonPaul A. Ellison - University of Wisconsin–MadisonTodd E. Barnhart - University of Wisconsin–MadisonDennis R. Elema - Technical University of DenmarkCharles P. Theuer - Tracon Pharmaceuticals (United States)Weibo Cai - University of Wisconsin–MadisonRobert J. Nickles - University of Wisconsin–MadisonGregory W. Severin - Technical University of Denmark
- Resource Type
- Journal article
- Publication Details
- Bioconjugate chemistry, Vol.26(10), pp.2118-2124
- DOI
- 10.1021/acs.bioconjchem.5b00414
- PMID
- 26317429
- PMCID
- PMC4618027
- NLM abbreviation
- Bioconjug Chem
- ISSN
- 1043-1802
- eISSN
- 1520-4812
- Publisher
- Amer Chemical Soc
- Number of pages
- 7
- Grant note
- DE-FG02-12ER41882 / DOE; United States Department of Energy (DOE) EU FP7 framework (MATHIAS) T32GM008349 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) DGE-1256259 / National Science Foundation; National Science Foundation (NSF) 5T32GM08349; 5 T32 CA009206-34; NIBIB/NCI 1R01CA169365; P30CA014520 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA University of Wisconsin - Madison T32CA009206 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) 125246-RSG-13-099-01-CCE / American Cancer Society
- Language
- English
- Date published
- 10/01/2015
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Radiation Oncology
- Record Identifier
- 9984383285802771
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