Chelation chemistry of manganese-52 for PET imaging applications

James M Omweri; Volkan Tekin; Shefali Saini; Hailey A Houson; Samith B Jayawardana; Daniel A Decato; Gayan B Wijeratne; Suzanne E Lapi

doi:10.1016/j.nucmedbio.2023.108874

Chelation chemistry of manganese-52 for PET imaging applications

Nucl Med Biol. 2024 Jan-Feb:128-129:108874. doi: 10.1016/j.nucmedbio.2023.108874. Epub 2023 Dec 23.

Authors

James M Omweri¹, Volkan Tekin², Shefali Saini¹, Hailey A Houson², Samith B Jayawardana³, Daniel A Decato⁴, Gayan B Wijeratne³, Suzanne E Lapi⁵

Affiliations

¹ Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL 35205, USA; Department of Radiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
² Department of Radiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
³ Department of Chemistry and Biochemistry, University of Alabama, Tuscaloosa, AL 35487, USA.
⁴ Department of Chemistry and Biochemistry, University of Montana, MT 59812, USA.
⁵ Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL 35205, USA; Department of Radiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address: lapi@uab.edu.

PMID: 38154167
DOI: 10.1016/j.nucmedbio.2023.108874

Abstract

Introduction: Due to its decay and chemical properties, interest in manganese-52 has increased for development of long-lived PET radiopharmaceuticals. Its long half-life of 5.6 days, low average positron energy (242 keV), and sufficient positron decay branching ratio make it suitable for radiolabeling macromolecules for investigating slow biological processes. This work aims to establish suitable chelators for manganese-52 that can be radiolabeled at mild conditions through the evaluation of commercially available chelators.

Methods: Manganese-52 was produced through the nuclear reaction ^NatCr(p,n)⁵²Mn by irradiation of natural chromium targets on a TR24 cyclotron followed by purification through ion exchange chromatography. The radiolabeling efficiencies of chelators: DOTA, DiAmsar, TETA, DO3A, NOTA, 4'-Formylbenzo-15-crown-5, Oxo-DO3A, and DFO, were assessed by investigating the impact of pH, buffer type, and temperature. In vitro stability of [⁵²Mn]Mn(DO3A)^-, [⁵²Mn]Mn(Oxo-DO3A)^-, and [⁵²Mn]Mn(DOTA)^2- were evaluated in mouse serum. The radiocomplexes were also evaluated in vivo in mice. Crystals of [Mn(Oxo-DO3A)]^- were synthesized by reacting Oxo-DO3A with MnCl₂ and characterized by single crystal X-ray diffraction.

Results: Yields of 185 ± 19 MBq (5.0 ± 0.5 mCi) (n = 4) of manganese-52 were produced at the end of a 4 h, 15 μA, bombardment with 12.5 MeV protons. NOTA, DO3A, DOTA, and Oxo-DO3A chelators were readily radiolabeled with >96 % radiochemical purity at all conditions. Manganese radiocomplexes of Oxo-DO3A, DOTA, and DO3A remained stable in vitro up to 5 days and exhibited different biodistribution profiles compared to [⁵²Mn]MnCl₂. The solid-state structure of Mn-Oxo-DO3A complex was determined by single-crystal X-ray diffraction.

Conclusions: DO3A and Oxo-DO3A are suitable chelators for manganese-52 which are readily radiolabeled at mild conditions with high molar activity, and demonstrate both in vitro and in vivo stability.

Keywords: Chelators; Ion exchange chromatography; Macromolecules; Manganese-52; Radiochemical yields; Radiolabeling; Radiopharmaceuticals.

MeSH terms

Animals
Chelating Agents / chemistry
Manganese*
Mice
Positron-Emission Tomography* / methods
Radioisotopes*
Radiopharmaceuticals / chemistry
Tissue Distribution

Substances

Manganese-52
Manganese
Radiopharmaceuticals
Chelating Agents
Radioisotopes