Microwave-assisted synthesis of [ 52 Mn]Mn-porphyrins: Applications in cell and liposome radiolabelling.

Autor: Gawne PJ; School of Biomedical Engineering and Imaging Sciences, King's College London, St Thomas' Hospital, London, UK., Pinto SMA; Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal., Nielsen KM; School of Biomedical Engineering and Imaging Sciences, King's College London, St Thomas' Hospital, London, UK., Keeling GP; School of Biomedical Engineering and Imaging Sciences, King's College London, St Thomas' Hospital, London, UK., Pereira MM; Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal., T M de Rosales R; School of Biomedical Engineering and Imaging Sciences, King's College London, St Thomas' Hospital, London, UK. Electronic address: rafael.torres@kcl.ac.uk.
Jazyk: angličtina
Zdroj: Nuclear medicine and biology [Nucl Med Biol] 2022 Nov-Dec; Vol. 114-115, pp. 6-17. Date of Electronic Publication: 2022 Sep 02.
DOI: 10.1016/j.nucmedbio.2022.08.006
Abstrakt: Background: Manganese porphyrins have several therapeutic/imaging applications, including their use as radioprotectants (in clinical trials) and as paramagnetic MRI contrast agents. The affinity of porphyrins for lipid bilayers also makes them candidates for cell/liposome labelling. We hypothesised that metalation with the positron emission tomography (PET) radionuclide 52 Mn (t 1/2  = 5.6 d) would allow long-term in vivo biodistribution studies of Mn-porphyrins, as well as a method to label and track cells/liposomes, but methods for fast and efficient radiolabelling are lacking.
Results: Several porphyrins were produced and radiolabelled by addition to neutralised [ 52 Mn]MnCl 2 and heating using a microwave (MW) synthesiser, and compared with non-MW heating. MW radiosynthesis allowed >95 % radiochemical yields (RCY) in just 1 h. Conversely, non-MW heating at 70 °C for 1 h resulted in low RCY (0-25 % RCY) and most porphyrins did not reach radiolabelling completion after 24 h. Formation of the 52 Mn-complexes were confirmed with radio-HPLC by comparison with their non-radioactive 55 Mn counterparts. Following this, several [ 52 Mn]Mn-porphyrins were used to radiolabel liposomes resulting in 75-86 % labelling efficiency (LE). Two lead [ 52 Mn]Mn-porphyrins were taken forward to label MDA-MB-231 cancer cells in vitro, achieving ca. 11 % LE. After 24 h, 32-45 % of the [ 52 Mn]Mn-porphyrins was retained in cells.
Conclusions: In contrast to standard methods, MW heating allows the fast synthesis of [ 52 Mn]Mn-porphyrins with >95 % radiochemical yields that avoid purification. [ 52 Mn]Mn-porphyrins also show promising cell/liposome labelling properties. Our reported technique can potentially be exploited for the in vivo imaging of Mn-porphyrin therapeutics, as well as for the accurate in vivo quantification of Mn-porphyrin MRI agents.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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