Synthesis and in vivo biological evaluation of 68Ga labelled carbonic anhydrase IX targeting small molecules for positron emission tomography

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dc.contributor.authorSneddon, Den_AU
dc.contributor.authorNiemans, Ren_AU
dc.contributor.authorBauwens, Men_AU
dc.contributor.authorYaromina, Aen_AU
dc.contributor.authorvan Kuijk, SJAen_AU
dc.contributor.authorLieuwes, NGen_AU
dc.contributor.authorBiemans, Ren_AU
dc.contributor.authorPooters, Ien_AU
dc.contributor.authorPellegrini, PAen_AU
dc.contributor.authorLengkeek, NAen_AU
dc.contributor.authorGreguric, Ien_AU
dc.contributor.authorTonissen, KRen_AU
dc.contributor.authorSupuran, CTen_AU
dc.contributor.authorLambin, Pen_AU
dc.contributor.authorDubois, Len_AU
dc.contributor.authorPoulsen, Sen_AU
dc.date.accessioned2020-03-23T01:48:20Zen_AU
dc.date.available2020-03-23T01:48:20Zen_AU
dc.date.issued2016-06-20en_AU
dc.date.statistics2020-03-20en_AU
dc.description.abstractTumor hypoxia contributes resistance to chemo- and radiotherapy, while oxygenated tumors are sensitive to these treatments. The indirect detection of hypoxic tumors is possible by targeting carbonic anhydrase IX (CA IX), an enzyme overexpressed in hypoxic tumors, with sulfonamide-based imaging agents. In this study, we present the design and synthesis of novel gallium-radiolabeled small-molecule sulfonamides targeting CA IX. The compounds display favorable in vivo pharmacokinetics and stability. We demonstrate that our lead compound, [68Ga]-2, discriminates CA IX-expressing tumors in vivo in a mouse xenograft model using positron emission tomography (PET). This compound shows specific tumor accumulation and low uptake in blood and clears intact to the urine. These findings were reproduced in a second study using PET/computed tomography. Small molecules investigated to date utilizing 68Ga for preclinical CA IX imaging are scarce, and this is one of the first effective 68Ga compounds reported for PET imaging of CA IX. © 2016 American Chemical Societyen_AU
dc.identifier.citationSneddon, D., Niemans, R., Bauwens, M., Yaromina, A., van Kuijk, S. J., Lieuwes, N. G., Biemand, R., Pooters, I., Pellegrini, P. A., Lengkeek, N. A., Greguric, I., Tonissen, K. F., Supuran, C. T., Lambin, P., Dubios, L., & Poulsen, S. (2016). Synthesis and in vivo biological evaluation of 68Ga-labeled carbonic anhydrase IX targeting small molecules for positron emission tomography. Journal of Medicinal Chemistry, 59(13), 6431-6443. doi:10.1021/acs.jmedchem.6b00623en_AU
dc.identifier.govdoc8879en_AU
dc.identifier.issn0022-2623en_AU
dc.identifier.issue13en_AU
dc.identifier.journaltitleJournal of Medicinal Chemistryen_AU
dc.identifier.pagination6431-6443en_AU
dc.identifier.urihttps://doi.org/10.1021/acs.jmedchem.6b00623en_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/9183en_AU
dc.identifier.volume59en_AU
dc.language.isoenen_AU
dc.publisherAmerican Chemical Societyen_AU
dc.subjectAnoxiaen_AU
dc.subjectPositron computed tomographyen_AU
dc.subjectRodentsen_AU
dc.subjectSulfonesen_AU
dc.subjectNeoplasmsen_AU
dc.subjectBlooden_AU
dc.subjectUrineen_AU
dc.titleSynthesis and in vivo biological evaluation of 68Ga labelled carbonic anhydrase IX targeting small molecules for positron emission tomographyen_AU
dc.typeJournal Articleen_AU
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