Journal article
Novel Preparation Methods of 52Mn for ImmunoPET Imaging
52Mn (t1/2 =5.59 d, ß+ = 29.6%, Eßave = 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 52Mn in a state suitable for macromolecule labeling.
To that end a 52Mn production, purification, and labeling system is presented, and its applicability in preclinical, macromolecule PET is shown using the conjugate 52Mn-DOTA-TRC105. 52Mn 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 semi-organic mobile phase, 97:3 (v:v) ethanol: HCl (11M, aqueous).
The method is 62 ± 14% efficient (n=7) in 52Mn recovery, leading to a separation factor from Cr of (1.6 ± 1.0) x106 (n = 4), and an average effective specific activity of 0.8 GBq/µmol (n = 4) in titration against DOTA. 52Mn-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 hours post injection and ex vivo 52Mn biodistribution validates the in vivo PET data. Free 52Mn2+(as chloride or acetate) is used as a control in additional mice to evaluate the non-targeted biodistribution in the tumor model.
Language: | English |
---|---|
Year: | 2015 |
Pages: | 2118-2124 |
ISSN: | 15204812 and 10431802 |
Types: | Journal article |
DOI: | 10.1021/acs.bioconjchem.5b00414 |
ORCIDs: | Fonslet, Jesper , Elema, Dennis Ringkjøbing and Severin, Gregory |
CD105/Endoglin DOTA chelation ImmunoPET Manganese-52 (Mn-52, 52Mn) Molecular imaging Organic anion exchange Positron emission tomography (PET) TRC105 Trace metal analysis (MP-AES, ICP-OES) Tumor angiogenesis
1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid Animals Antibodies, Monoclonal Chromium Female Heterocyclic Compounds, 1-Ring Isotope Labeling Magnetic Resonance Imaging Manganese Mice, Inbred BALB C Positron-Emission Tomography Radiochemistry Radioisotopes Radiopharmaceuticals Tissue Distribution Xenograft Model Antitumor Assays carotuximab