@article{d9f6d00db5ef4ee981c722dfca00a3f8,
title = "In Vivo Trafficking of the Anticancer Drug Tris(8-Quinolinolato) Gallium (III) (KP46) by Gallium-68/67 PET/SPECT Imaging",
abstract = "KP46 (tris(hydroxyquinolinato)gallium(III)) is an experimental, orally administered anticancer drug. Its absorption, delivery to tumours, and mode of action are poorly understood. We aimed to gain insight into these issues using gallium-67 and gallium-68 as radiotracers with SPECT and PET imaging in mice. [67Ga]KP46 and [68Ga]KP46, compared with [68Ga]gallium acetate, were used for logP measurements, in vitro cell uptake studies in A375 melanoma cells, and in vivo imaging in mice bearing A375 tumour xenografts up to 48 h after intravenous (tracer level) and oral (tracer and bulk) administration. 68Ga was more efficiently accumulated in A375 cells in vitro when presented as [68Ga]KP46 than as [68Ga]gallium acetate, but the reverse was observed when intravenously administered in vivo. After oral administration of [68/67Ga]KP46, absorption of 68Ga and 67Ga from the GI tract and delivery to tumours were poor, with the majority excreted in faeces. By 48 h, low but measurable amounts were accumulated in tumours. The distribution in tissues of absorbed radiogallium and octanol extraction of tissues suggested trafficking as free gallium rather than as KP46. We conclude that KP46 likely acts as a slow releaser of gallium ions which are inefficiently absorbed from the GI tract and trafficked to tissues, including tumour and bone.",
keywords = "8-hydroxyquinoline, cancer, gallium, KP46, PET imaging, radionuclide imaging, SPECT imaging",
author = "Darwesh, {Afnan M.F.} and Cinzia Imberti and Bartnicka, {Joanna J.} and Fahad Al-Salemee and Blower, {Julia E.} and Alex Rigby and Jayanta Bordoloi and Alex Griffiths and Ma, {Michelle T.} and Blower, {Philip J.}",
note = "Funding Information: We acknowledge support from the Centre for Medical Engineering at King{\textquoteright}s College London funded by the Wellcome Trust and EPSRC (203148/Z/16/Z), the Wellcome Multiuser Equipment Radioanalytical Facility funded by Wellcome Trust (212885/Z/18/Z), and the EPSRC programme for Next Generation Molecular Imaging and Therapy with Radionuclides (EP/S03279/1 {\textquoteleft}MITHRAS{\textquoteright}). ICP-MS measurements were made possible by the London Metallomics Facility funded by Wellcome Multiuser Equipment grant 202902/Z/16/Z. Z.Y. and C.I. were supported by the NIHR Biomedical Research Centre award to Guy{\textquoteright}s and St Thomas{\textquoteright}s NHS Foundation Trust in partnership with King{\textquoteright}s College London and King{\textquoteright}s College Hospital NHS Foundation Trust. F.A.S. was supported by the CRUK City of London Centre Award [C7893/A26233]. J.J.B. was supported by a studentship from the MRC Doctoral Training Partnership at King{\textquoteright}s College London. A.D. was supported by King Abdulaziz University and the Saudi Arabian Cultural Bureau in the UK. No other potential conflicts of interest relevant to this article were reported. Publisher Copyright: {\textcopyright} 2023 by the authors.",
year = "2023",
month = oct,
doi = "10.3390/molecules28207217",
language = "English",
volume = "28",
journal = "Molecules",
issn = "1420-3049",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "20",
}
