title: Microwave gallium-68 radiochemistry for kinetically stable bis(thiosemicarbazone) complexes: structural investigations and cellular uptake under hypoxia.
abstract: We report the microwave synthesis of several bis(thiosemicarbazones) and the rapid gallium-68 incorporation to give the corresponding metal complexes. These proved kinetically stable under 'cold' and 'hot' biological assays and were investigated using laser scanning confocal microscopy, flow cytometry and radioactive cell retention studies under normoxia and hypoxia. (68)Ga complex retention was found to be 34% higher in hypoxic cells than in normoxic cells over 30 min, further increasing to 53% at 120 min. Our data suggests that this class of gallium complexes show hypoxia selectivity suitable for imaging in living cells and in vivo tests by microPET in nude athymic mice showed that they are excreted within 1 h of their administration.
authors.affiliation: Department of Medicine, Imperial College, Du Cane Road, W12 0NN, London, UK. l.carroll@imperial.ac.uk eric.aboagye@imperial.ac.uk.
authors.forename: Israt S
authors.initials: IS
authors.lastname: Alam
authors.affiliation: Department of Chemistry, University of Bath, Claverton Down, BA2 7AY, UK. s.pascu@bath.ac.uk.
authors.forename: Rory L
authors.initials: RL
authors.lastname: Arrowsmith
authors.affiliation: Department of Chemistry, University of Bath, Claverton Down, BA2 7AY, UK. s.pascu@bath.ac.uk.
authors.forename: Fernando
authors.initials: F
authors.lastname: Cortezon-Tamarit
authors.affiliation: Department of Medicine, Imperial College, Du Cane Road, W12 0NN, London, UK. l.carroll@imperial.ac.uk eric.aboagye@imperial.ac.uk.
authors.forename: Frazer
authors.initials: F
authors.lastname: Twyman
authors.affiliation: Department of Chemistry, University of Bath, Claverton Down, BA2 7AY, UK. s.pascu@bath.ac.uk.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Kociok-Köhn
authors.affiliation: Oxford Brookes University, Faculty of Health and Life Sciences, The Science and Technology Facilities Council, Rutherford Appleton Laboratory, Harwell, Oxford, UK.
authors.forename: Stanley W
authors.initials: SW
authors.lastname: Botchway
authors.affiliation: Inorganic Chemistry Laboratory, South Parks Road, Oxford OX2 6TT, UK.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Dilworth
authors.affiliation: Department of Medicine, Imperial College, Du Cane Road, W12 0NN, London, UK. l.carroll@imperial.ac.uk eric.aboagye@imperial.ac.uk.
authors.forename: Laurence
authors.initials: L
authors.lastname: Carroll
authors.affiliation: Department of Medicine, Imperial College, Du Cane Road, W12 0NN, London, UK. l.carroll@imperial.ac.uk eric.aboagye@imperial.ac.uk.
authors.forename: Eric O
authors.initials: EO
authors.lastname: Aboagye
authors.affiliation: Department of Chemistry, University of Bath, Claverton Down, BA2 7AY, UK. s.pascu@bath.ac.uk.
authors.forename: Sofia I
authors.initials: SI
authors.lastname: Pascu
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D005708:Gallium; D005710:Gallium Radioisotopes / Q000737:chemistry* / Q000493:pharmacokinetics*; D006801:Humans; D000860:Hypoxia / Q000175:diagnosis; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D008872:Microwaves; D008958:Models, Molecular; D061848:Optical Imaging; D049268:Positron-Emission Tomography; D013050:Spectrometry, Fluorescence; D013882:Thiosemicarbazones / Q000737:chemistry* / Q000493:pharmacokinetics*
chemical_list: D005710:Gallium Radioisotopes; D013882:Thiosemicarbazones; D005708:Gallium