Exploratory Analysis of Serial <sup>18</sup>F-fluciclovine PET-CT and Multiparametric MRI during Chemoradiation for Glioblastoma

Kavi Fatania; Russell Frood; Marcus Tyyger; Garry McDermott; Sharon Fernandez; Gary C. Shaw; Marjorie Boissinot; Daniela Salvatore; Luisa Ottobrini; Irvin Teh; John Wright; Marc A. Bailey; Joanna Koch-Paszkowski; Jurgen E. Schneider; David L. Buckley; Louise Murray; Andrew Scarsbrook; Susan C. Short; Stuart Currie

doi:10.3390/cancers14143485

Cancers (Jul 2022)

Exploratory Analysis of Serial <sup>18</sup>F-fluciclovine PET-CT and Multiparametric MRI during Chemoradiation for Glioblastoma

Kavi Fatania,
Russell Frood,
Marcus Tyyger,
Garry McDermott,
Sharon Fernandez,
Gary C. Shaw,
Marjorie Boissinot,
Daniela Salvatore,
Luisa Ottobrini,
Irvin Teh,
John Wright,
Marc A. Bailey,
Joanna Koch-Paszkowski,
Jurgen E. Schneider,
David L. Buckley,
Louise Murray,
Andrew Scarsbrook,
Susan C. Short,
Stuart Currie

Affiliations

Kavi Fatania: Department of Radiology, Leeds Teaching Hospitals Trust, Leeds General Infirmary, Leeds LS1 3EX, UK
Russell Frood: Department of Radiology, Leeds Teaching Hospitals Trust, Leeds General Infirmary, Leeds LS1 3EX, UK
Marcus Tyyger: Department of Medical Physics, Leeds Teaching Hospitals Trust, St James’s University Hospital, Leeds LS9 7TF, UK
Garry McDermott: Department of Medical Physics, Leeds Teaching Hospitals Trust, St James’s University Hospital, Leeds LS9 7TF, UK
Sharon Fernandez: Department of Clinical Oncology, Leeds Teaching Hospitals Trust, St James’s University Hospital, Leeds LS9 7TF, UK
Gary C. Shaw: Leeds Institute of Medical Research, University of Leeds, Leeds LS2 9TJ, UK
Marjorie Boissinot: Leeds Institute of Medical Research, University of Leeds, Leeds LS2 9TJ, UK
Daniela Salvatore: Department of Pathophysiology and Transplantation, University of Milan, 20122 Segrate, Italy
Luisa Ottobrini: Department of Pathophysiology and Transplantation, University of Milan, 20122 Segrate, Italy
Irvin Teh: Biomedical Imaging Science Department, and Discovery & Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9TJ, UK
John Wright: Biomedical Imaging Science Department, and Discovery & Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9TJ, UK
Marc A. Bailey: Biomedical Imaging Science Department, and Discovery & Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9TJ, UK
Joanna Koch-Paszkowski: Biomedical Imaging Science Department, and Discovery & Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9TJ, UK
Jurgen E. Schneider: Biomedical Imaging Science Department, and Discovery & Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9TJ, UK
David L. Buckley: Biomedical Imaging Science Department, and Discovery & Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9TJ, UK
Louise Murray: Leeds Institute of Medical Research, University of Leeds, Leeds LS2 9TJ, UK
Andrew Scarsbrook: Department of Radiology, Leeds Teaching Hospitals Trust, Leeds General Infirmary, Leeds LS1 3EX, UK
Susan C. Short: Leeds Institute of Medical Research, University of Leeds, Leeds LS2 9TJ, UK
Stuart Currie: Department of Radiology, Leeds Teaching Hospitals Trust, Leeds General Infirmary, Leeds LS1 3EX, UK

DOI: https://doi.org/10.3390/cancers14143485
Journal volume & issue: Vol. 14, no. 14
p. 3485

Abstract

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Anti-1-amino-3-18fluorine-fluorocyclobutane-1-carboxylic acid (18F-fluciclovine) positron emission tomography (PET) shows preferential glioma uptake but there is little data on how uptake correlates with post-contrast T1-weighted (Gd-T1) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) activity during adjuvant treatment. This pilot study aimed to compare 18F-fluciclovine PET, DCE-MRI and Gd-T1 in patients undergoing chemoradiotherapy for glioblastoma (GBM), and in a parallel pre-clinical GBM model, to investigate correlation between 18F-fluciclovine uptake, MRI findings, and tumour biology. 18F-fluciclovine-PET-computed tomography (PET-CT) and MRI including DCE-MRI were acquired before, during and after adjuvant chemoradiotherapy (60 Gy in 30 fractions with temozolomide) in GBM patients. MRI volumes were manually contoured; PET volumes were defined using semi-automatic thresholding. The similarity of the PET and DCE-MRI volumes outside the Gd-T1 volume boundary was measured using the Dice similarity coefficient (DSC). CT-2A tumour-bearing mice underwent MRI and 18F-fluciclovine PET-CT. Post-mortem mice brains underwent immunohistochemistry staining for ASCT2 (amino acid transporter), nestin (stemness) and Ki-67 (proliferation) to assess for biologically active tumour. 6 patients were recruited (GBM 1–6) and grouped according to overall survival (OS)—short survival (GBM-SS, median OS 249 days) and long survival (GBM-LS, median 903 days). For GBM-SS, PET tumour volumes were greater than DCE-MRI, in turn greater than Gd-T1. For GBM-LS, Gd-T1 and DCE-MRI were greater than PET. Tumour-specific 18F-fluciclovine uptake on pre-clinical PET-CT corresponded to immunostaining for Ki-67, nestin and ASCT2. Results suggest volumes of 18F-fluciclovine-PET activity beyond that depicted by DCE-MRI and Gd-T1 are associated with poorer prognosis in patients undergoing chemoradiotherapy for GBM. The pre-clinical model confirmed 18F-fluciclovine uptake reflected biologically active tumour.

Published in Cancers

ISSN: 2072-6694 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.mdpi.com/journal/cancers/

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