Targeted beta therapy of prostate cancer with 177 Lu-labelled Miltuximab® antibody against glypican-1 (GPC-1).

Autor: Yeh MC; Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, 37 Kent Street, Woolloongabba, Queensland, 4102, Australia., Tse BWC; Preclinical Imaging Facility, Translational Research Institute, 37 Kent Street, Woolloongabba, Queensland, 4102, Australia., Fletcher NL; Centre for Advanced Imaging, Australian Institute for Bioengineering and Nanotechnology, ARC Centre of Excellence in Convergent Bio-Nano Science and Technology and ARC Training Centre in Biomedical Imaging Technology, University of Queensland, Building 57 University Drive, St Lucia, Queensland, 4072, Australia., Houston ZH; Centre for Advanced Imaging, Australian Institute for Bioengineering and Nanotechnology, ARC Centre of Excellence in Convergent Bio-Nano Science and Technology and ARC Training Centre in Biomedical Imaging Technology, University of Queensland, Building 57 University Drive, St Lucia, Queensland, 4072, Australia., Lund M; Glytherix Ltd, Suite 2, Ground Floor 75 Talavera Road, Macquarie Park, New South Wales, 2113, Australia., Volpert M; Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, 37 Kent Street, Woolloongabba, Queensland, 4102, Australia., Stewart C; Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, 37 Kent Street, Woolloongabba, Queensland, 4102, Australia., Sokolowski KA; Preclinical Imaging Facility, Translational Research Institute, 37 Kent Street, Woolloongabba, Queensland, 4102, Australia., Jeet V; Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, 37 Kent Street, Woolloongabba, Queensland, 4102, Australia., Thurecht KJ; Centre for Advanced Imaging, Australian Institute for Bioengineering and Nanotechnology, ARC Centre of Excellence in Convergent Bio-Nano Science and Technology and ARC Training Centre in Biomedical Imaging Technology, University of Queensland, Building 57 University Drive, St Lucia, Queensland, 4072, Australia., Campbell DH; Glytherix Ltd, Suite 2, Ground Floor 75 Talavera Road, Macquarie Park, New South Wales, 2113, Australia., Walsh BJ; Glytherix Ltd, Suite 2, Ground Floor 75 Talavera Road, Macquarie Park, New South Wales, 2113, Australia., Nelson CC; Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, 37 Kent Street, Woolloongabba, Queensland, 4102, Australia., Russell PJ; Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, 37 Kent Street, Woolloongabba, Queensland, 4102, Australia. pamela.russell@qut.edu.au.
Jazyk: angličtina
Zdroj: EJNMMI research [EJNMMI Res] 2020 May 07; Vol. 10 (1), pp. 46. Date of Electronic Publication: 2020 May 07.
DOI: 10.1186/s13550-020-00637-x
Abstrakt: Purpose: Chimeric antibody Miltuximab®, a human IgG1 engineered from the parent antibody MIL-38, is in clinical development for solid tumour therapy. Miltuximab® targets glypican-1 (GPC-1), a cell surface protein involved in tumour growth, which is overexpressed in solid tumours, including prostate cancer (PCa). This study investigated the potential of 89 Zr-labelled Miltuximab® as an imaging agent, and 177 Lu-labelled Miltuximab® as a targeted beta therapy, in a mouse xenograft model of human prostate cancer.
Methods: Male BALB/c nude mice were inoculated subcutaneously with GPC-1-positive DU-145 PCa cells. In imaging and biodistribution studies, mice bearing palpable tumours received (a) 2.62 MBq [ 89 Zr]Zr-DFO-Miltuximab® followed by PET-CT imaging, or (b) 6 MBq [ 177 Lu]Lu-DOTA-Miltuximab® by Cerenkov imaging, and ex vivo assessment of biodistribution. In an initial tumour efficacy study, mice bearing DU-145 tumours were administered intravenously with 6 MBq [ 177 Lu]Lu-DOTA-Miltuximab® or control DOTA-Miltuximab® then euthanised after 27 days. In a subsequent survival efficacy study, tumour-bearing mice were given 3 or 10 MBq of [ 177 Lu]Lu-DOTA-Miltuximab®, or control, and followed up to 120 days.
Results: Antibody accumulation in DU-145 xenografts was detected by PET-CT imaging using [ 89 Zr]Zr-DFO-Miltuximab® and confirmed by Cerenkov luminescence imaging post injection of [ 177 Lu]Lu-DOTA-Miltuximab®. Antibody accumulation was higher (% IA/g) in tumours than other organs across multiple time points. A single injection with 6 MBq of [ 177 Lu]Lu-DOTA-Miltuximab® significantly inhibited tumour growth as compared with DOTA-Miltuximab® (control). In the survival study, mice treated with 10 MBq [ 177 Lu]Lu-DOTA-Miltuximab® had significantly prolonged survival (mean 85 days) versus control (45 days), an effect associated with increased cancer cell apoptosis. Tissue histopathology assessment showed no abnormalities associated with [ 177 Lu]Lu-DOTA-Miltuximab®, in line with other observations of tolerability, including body weight stability.
Conclusion: These findings demonstrate the potential utility of Miltuximab® as a PET imaging agent ([ 89 Zr]Zr-DFO-Miltuximab®) and a beta therapy ([ 177 Lu]Lu-DOTA-Miltuximab®) in patients with PCa or other GPC-1 expressing tumours.
Databáze: MEDLINE
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