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Suppression of tumour growth from transplanted astrocytoma cells transfected with luciferase in mice by bioluminescence mediated, systemic, photodynamic therapy

Ng, Jane; Henriquez, Nico; Kitchen, Neil; Williams, Norman; Novelli, Marco; Oukrif, Dahmane; Macrobert, Alexander; (2024) Suppression of tumour growth from transplanted astrocytoma cells transfected with luciferase in mice by bioluminescence mediated, systemic, photodynamic therapy. Photodiagnosis and Photodynamic Therapy , 45 , Article 103923. 10.1016/j.pdpdt.2023.103923. Green open access

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Abstract

Background: Grade 4 astrocytomas are usually incurable due to their diffusely infiltrative nature. Photodynamic therapy (PDT) is a promising therapeutic option, but external light delivery is impractical when cancer cells infiltrate unknown areas of normal brain. Hence the search for endogenous sources to generate light at cancer cells. In vitro, astrocytoma cells, transfected with firefly luciferase, can be killed by bioluminescence-mediated PDT (bPDT). This study asks if bPDT can suppress tumour growth In vivo, when all components of treatment are administered systemically. Methods: Transfected astrocytoma cells were injected subcutaneously or intra-cranially in athymic CD1 nu/nu mice. bPDT required ip bolus of mTHPC (photosensitiser) and delivery of the D-luciferin substrate over 7 days via an implanted osmotic pump. Control animals had no treatment, photosensitiser only or D-luciferin only. For subcutaneous tumours, size and BLI (light emitted after D-luciferin bolus) were measured before and every 2 days after PDT. For intracranial tumours, monitoring was weekly BLI. Results: For subcutaneous tumours, there was significant suppression of the tumour growth rate (P<0.05), and absolute tumour size (P<0.01) after bPDT. Proliferation of subcutaneous and intracranial tumours (monitored by BrdU uptake) was significantly reduced in treated mice. (P<0.001) Conclusions: This study reports bPDT suppression of tumour growth from luciferase transfected astrocytoma cells with all components of treatment given systemically, as required for effective management of recurrent astrocytomas in unknown sites. However, research on systemic bPDT is needed to establish whether effects on non-transfected tumours can be achieved without any unacceptable effects on normal tissues.

Type: Article
Title: Suppression of tumour growth from transplanted astrocytoma cells transfected with luciferase in mice by bioluminescence mediated, systemic, photodynamic therapy
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.pdpdt.2023.103923
Publisher version: https://doi.org/10.1016/j.pdpdt.2023.103923
Language: English
Additional information: © 2023 The Author(s). Published by Elsevier B.V. under a Creative Commons license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Pathology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Targeted Intervention
URI: https://discovery.ucl.ac.uk/id/eprint/10212215
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