Working Paper
Authors
- Peter J. Gawne
King's College London ,
- Sara M. A. Pinto University of Coimbra ,
- Karin M. Nielsen King's College London ,
- George P. Keeling King's College London ,
- Mariette M. Pereira University of Coimbra ,
- Rafael T. M. de Rosales King's College London
Abstract
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 52Mn (t1/2 = 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.
Several porphyrins were produced and radiolabelled by addition to neutralised [52Mn]MnCl2 and heated 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 oC for 1 h resulted in low RCY (0 – 25 % RCY) and most porphyrins did not reach radiolabelling completion after 24 h. Formation of the 52Mn-complexes were confirmed with radio-HPLC by comparison with their non-radioactive 55Mn counterparts. Following this, several 52Mn-porphyrins were used to radiolabel liposomes resulting in 75 – 86 % labelling efficiency (LE). Two lead 52Mn-porphyrins were taken forward to label MDA-MB-231 cancer cells in vitro, achieving ca. 11 % LE. After 24 h, 32 – 45 % of the 52Mn-porphyrin was retained in cells.
In contrast to standard methods, MW heating allows the fast synthesis of 52Mn-porphyrins with >95% radiochemical yields that avoid purification. 52Mn-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.
Version notes
We have added additional characterisation of the porphyrins and manganese porphyrins.
Content

Supplementary material

Electronic Supplementary Information
Details of synthesis, characterisation and stability of poprhyrins and manganese porphyrins