In Vivo Trafficking of the Anticancer Drug Tris(8-Quinolinolato) Gallium (III) (KP46) by Gallium-68/67 PET/SPECT Imaging

Afnan M.F. Darwesh, Cinzia Imberti, Joanna J. Bartnicka, Fahad Al-Salemee, Julia E. Blower, Alex Rigby, Jayanta Bordoloi, Alex Griffiths, Michelle T. Ma, Philip J. Blower*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number7217
JournalMolecules
Volume28
Issue number20
DOIs
Publication statusPublished - Oct 2023

Keywords

  • 8-hydroxyquinoline
  • cancer
  • gallium
  • KP46
  • PET imaging
  • radionuclide imaging
  • SPECT imaging

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