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Microwave gallium-68 radiochemistry for kinetically stable bis(thiosemicarbazone) complexes: structural investigations and cellular uptake under hypoxia

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 cytomet...

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Autores principales: Alam, Israt S., Arrowsmith, Rory L., Cortezon-Tamarit, Fernando, Twyman, Frazer, Kociok-Köhn, Gabriele, Botchway, Stanley W., Dilworth, Jonathan R., Carroll, Laurence, Aboagye, Eric O., Pascu, Sofia I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4758186/
https://www.ncbi.nlm.nih.gov/pubmed/26583314
http://dx.doi.org/10.1039/c5dt02537k
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author Alam, Israt S.
Arrowsmith, Rory L.
Cortezon-Tamarit, Fernando
Twyman, Frazer
Kociok-Köhn, Gabriele
Botchway, Stanley W.
Dilworth, Jonathan R.
Carroll, Laurence
Aboagye, Eric O.
Pascu, Sofia I.
author_facet Alam, Israt S.
Arrowsmith, Rory L.
Cortezon-Tamarit, Fernando
Twyman, Frazer
Kociok-Köhn, Gabriele
Botchway, Stanley W.
Dilworth, Jonathan R.
Carroll, Laurence
Aboagye, Eric O.
Pascu, Sofia I.
author_sort Alam, Israt S.
collection PubMed
description 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.
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spelling pubmed-47581862016-03-07 Microwave gallium-68 radiochemistry for kinetically stable bis(thiosemicarbazone) complexes: structural investigations and cellular uptake under hypoxia Alam, Israt S. Arrowsmith, Rory L. Cortezon-Tamarit, Fernando Twyman, Frazer Kociok-Köhn, Gabriele Botchway, Stanley W. Dilworth, Jonathan R. Carroll, Laurence Aboagye, Eric O. Pascu, Sofia I. Dalton Trans Chemistry 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. Royal Society of Chemistry 2016-01-07 2015-11-19 /pmc/articles/PMC4758186/ /pubmed/26583314 http://dx.doi.org/10.1039/c5dt02537k Text en This journal is © The Royal Society of Chemistry 2015 https://creativecommons.org/licenses/by/3.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/ (https://creativecommons.org/licenses/by/3.0/) ) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Chemistry
Alam, Israt S.
Arrowsmith, Rory L.
Cortezon-Tamarit, Fernando
Twyman, Frazer
Kociok-Köhn, Gabriele
Botchway, Stanley W.
Dilworth, Jonathan R.
Carroll, Laurence
Aboagye, Eric O.
Pascu, Sofia I.
Microwave gallium-68 radiochemistry for kinetically stable bis(thiosemicarbazone) complexes: structural investigations and cellular uptake under hypoxia
title Microwave gallium-68 radiochemistry for kinetically stable bis(thiosemicarbazone) complexes: structural investigations and cellular uptake under hypoxia
title_full Microwave gallium-68 radiochemistry for kinetically stable bis(thiosemicarbazone) complexes: structural investigations and cellular uptake under hypoxia
title_fullStr Microwave gallium-68 radiochemistry for kinetically stable bis(thiosemicarbazone) complexes: structural investigations and cellular uptake under hypoxia
title_full_unstemmed Microwave gallium-68 radiochemistry for kinetically stable bis(thiosemicarbazone) complexes: structural investigations and cellular uptake under hypoxia
title_short Microwave gallium-68 radiochemistry for kinetically stable bis(thiosemicarbazone) complexes: structural investigations and cellular uptake under hypoxia
title_sort microwave gallium-68 radiochemistry for kinetically stable bis(thiosemicarbazone) complexes: structural investigations and cellular uptake under hypoxia
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4758186/
https://www.ncbi.nlm.nih.gov/pubmed/26583314
http://dx.doi.org/10.1039/c5dt02537k
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