Exploratory Analysis of Serial 18F-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

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

Cancers (Basel). 2022 Jul 18;14(14):3485. doi: 10.3390/cancers14143485.

Authors

Kavi Fatania^{1

2}, Russell Frood¹, Marcus Tyyger³, Garry McDermott³, Sharon Fernandez⁴, Gary C Shaw², Marjorie Boissinot², Daniela Salvatore⁵, Luisa Ottobrini^{5

6}, Irvin Teh⁷, John Wright⁷, Marc A Bailey^{7

8}, Joanna Koch-Paszkowski⁷, Jurgen E Schneider⁷, David L Buckley⁷, Louise Murray^{2

4}, Andrew Scarsbrook^{1

2}, Susan C Short^{2

4}, Stuart Currie^{1

2}

Affiliations

¹ Department of Radiology, Leeds Teaching Hospitals Trust, Leeds General Infirmary, Leeds LS1 3EX, UK.
² Leeds Institute of Medical Research, University of Leeds, Leeds LS2 9TJ, UK.
³ Department of Medical Physics, Leeds Teaching Hospitals Trust, St James's University Hospital, Leeds LS9 7TF, UK.
⁴ Department of Clinical Oncology, Leeds Teaching Hospitals Trust, St James's University Hospital, Leeds LS9 7TF, UK.
⁵ Department of Pathophysiology and Transplantation, University of Milan, 20122 Segrate, Italy.
⁶ Institute of Molecular Bioimaging and Physiology, National Research Council (IBFM-CNR), 20054 Segrate, Italy.
⁷ Biomedical Imaging Science Department, and Discovery & Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9TJ, UK.
⁸ Leeds Vascular Institute, Leeds Teaching Hospitals Trust, Leeds General Infirmary, Leeds LS1 3EX, UK.

Abstract

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.

Keywords: adjuvant; amino acid transport systems; chemoradiotherapy; glioblastoma; magnetic resonance imaging; positron-emission tomography.

Abstract

Grants and funding