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Title: Synthesis and in vivo biological evaluation of 68Ga labelled carbonic anhydrase IX targeting small molecules for positron emission tomography
Authors: Sneddon, D
Niemans, R
Bauwens, M
Yaromina, A
van Kuijk, SJA
Lieuwes, NG
Biemans, R
Pooters, I
Pellegrini, PA
Lengkeek, NA
Greguric, I
Tonissen, KR
Supuran, CT
Lambin, P
Dubois, L
Poulsen, S
Keywords: Anoxia
Positron computed tomography
Issue Date: 20-Jun-2016
Publisher: American Chemical Society
Citation: Sneddon, 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.6b00623
Abstract: Tumor 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 Society
Gov't Doc #: 8879
ISSN: 0022-2623
Appears in Collections:Journal Articles

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