High folate receptor expression in gliomas can be detected in vivo using folate-based positron emission tomography with high tumor-to-brain uptake ratio divulging potential future targeting possibilities

Frontiers in Immunology

Immunology

Johan Rajander¹  Nathan A. Cleveland²  Philip S. Low²  Hasan Mansour A Mansour²  Maria Gardberg³  Maxwell W. G. Miner⁴  Riikka Viitanen⁴  Salli Kärnä⁴  Piritta Saipa⁴  Jenni Virta⁴  Petri Elo⁴  Xiang-Guo Li⁵  Heidi Liljenbäck⁶  Anne Roivainen⁷  Jarmo Teuho⁸ 

[1] Accelerator Laboratory, Turku PET Centre, Åbo Akademi University, Turku, Finland;Department of Chemistry, Purdue University, West Lafayette, IN, United States;Department of Pathology, Turku University Hospital and Institute of Biomedicine, University of Turku, Turku, Finland;Turku PET Centre, University of Turku, Turku, Finland;Turku PET Centre, University of Turku, Turku, Finland;Department of Chemistry, University of Turku, Turku, Finland;InFLAMES Research Flagship Center, University of Turku, Turku, Finland;Turku PET Centre, University of Turku, Turku, Finland;Turku Center for Disease Modeling, University of Turku, Turku, Finland;Turku PET Centre, University of Turku, Turku, Finland;Turku Center for Disease Modeling, University of Turku, Turku, Finland;Turku PET Centre, Turku University Hospital, Turku, Finland;InFLAMES Research Flagship Center, University of Turku, Turku, Finland;Turku PET Centre, University of Turku, Turku, Finland;Turku PET Centre, Turku University Hospital, Turku, Finland;Department of Medical Physics, Turku University Hospital, Turku, Finland;

关键词: fluorine-18;    folate receptor;    glioma;    PET;    F-labelled folate;    brain tumor;   

DOI  :  10.3389/fimmu.2023.1145473

 received in 2023-01-16, accepted in 2023-04-28,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionNon-invasive imaging techniques such as positron emission tomography (PET) are extremely important for cancer detection and characterization especially for difficult to biopsy or extremely delicate organs such as the brain. The folate analogue 1,4,7-triazacylononane-1,4,7-triacetic acid-conjugated folate radiolabeled with aluminum fluoride-18 ([18F]FOL) has been previously shown to accumulate preferentially in tumor cells with an overexpression of folate receptors (FRs) and here was investigated for its ability to detect orthotopic gliomas in a rat model. In addition, we studied the expression of FRs in human glioblastoma samples to investigate if an analogous relationship may exist.MethodsNine BDIX rats were injected with BT4C rat glioma cells into the right hemisphere of the brain. Animals were imaged with gadolinium-enhanced magnetic resonance imaging at on days prior to PET/computed tomography (CT) imaging. Animals were divided into two groups, and were PET/CT imaged with either [18F]FOL or 2-deoxy-2-18F-fluoro-D-glucose ([18F]FDG) on 19 and 32-days post glioma grafting. Two subjects were also PET/CT imaged with [18F]FOL on day 16. Biodistribution was studied and brains were cryosectioned for autoradiography, immunofluorescence, and histological studies. Patient-derived paraffin-embedded glioblastomas were sectioned and stained with similar methods.ResultsPET imaging showed an increase of [18F]FOL tumor-to-brain uptake ratio (TBR) over the study duration from day 16/19 (3.3 ± 0.9) increasing to 5.7 ± 1.0 by day 32. [18F]FDG PET-imaged rats had a consistent TBR of 1.6 ± 0.1 throughout the study. Ex vivo autoradiography results revealed an exceptionally high TBR of 116.1 ± 26.9 for [18F]FOL while the [18F]FDG values were significantly lower giving 2.9 ± 0.6 (P<0.0001). Immunostaining demonstrated an increased presence of FR-α in the BT4C gliomas versus the contralateral brain tissue, while FR-β was present only on glioma periphery. Human sections assayed showed similar FRs expression characteristics.ConclusionThis study shows upregulation of FR-α inside glioma regions in both human and animal tissue, providing a biochemical basis for the observed increased [18F]FOL uptake in animal PET images. These results suggest that FRs targeting imaging and therapeutic compounds may possess clinically relevant translational abilities for the detection and treatment of gliomas.

【 授权许可】

Unknown   
Copyright © 2023 Miner, Liljenbäck, Virta, Kärnä, Viitanen, Elo, Gardberg, Teuho, Saipa, Rajander, Mansour, Cleveland, Low, Li and Roivainen