title: Preclinical TSPO Ligand PET to Visualize Human Glioma Xenotransplants: A Preliminary Study.
abstract: Current positron emission tomography (PET) imaging biomarkers for detection of infiltrating gliomas are limited. Translocator protein (TSPO) is a novel and promising biomarker for glioma PET imaging. To validate TSPO as a potential target for molecular imaging of glioma, TSPO expression was assayed in a tumor microarray containing 37 high-grade (III, IV) gliomas. TSPO staining was detected in all tumor specimens. Subsequently, PET imaging was performed with an aryloxyanilide-based TSPO ligand, [18F]PBR06, in primary orthotopic xenograft models of WHO grade III and IV gliomas. Selective uptake of [18F]PBR06 in engrafted tumor was measured. Furthermore, PET imaging with [18F]PBR06 demonstrated infiltrative glioma growth that was undetectable by traditional magnetic resonance imaging (MRI). Preliminary PET with [18F]PBR06 demonstrated a preferential tumor-to-normal background ratio in comparison to 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG). These results suggest that TSPO PET imaging with such high-affinity radiotracers may represent a novel strategy to characterize distinct molecular features of glioma growth, as well as better define the extent of glioma infiltration for therapeutic purposes.
authors.affiliation: Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center, Nashville, TN, United States of America.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Buck
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America.
authors.forename: Eliot T
authors.initials: ET
authors.lastname: McKinley
authors.affiliation: Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center, Nashville, TN, United States of America.
authors.forename: Allie
authors.initials: A
authors.lastname: Fu
authors.affiliation: Department of Pathology, Vanderbilt University Medical Center, Nashville, TN, United States of America.
authors.forename: Ty W
authors.initials: TW
authors.lastname: Abel
authors.affiliation: Vanderbilt-Ingram Cancer Center (VICC), Vanderbilt University Medical Center, Nashville, TN, United States of America; Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN, United States of America.
authors.forename: Reid C
authors.initials: RC
authors.lastname: Thompson
authors.affiliation: Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN, United States of America.
authors.forename: Lola
authors.initials: L
authors.lastname: Chambless
authors.affiliation: Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center, Nashville, TN, United States of America; Program in Chemical and Physical Biology, Vanderbilt University Medical Center, Nashville, TN, United States of America.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Watchmaker
authors.affiliation: Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, United States of America.
authors.forename: James P
authors.initials: JP
authors.lastname: Harty
authors.affiliation: Vanderbilt-Ingram Cancer Center (VICC), Vanderbilt University Medical Center, Nashville, TN, United States of America; Neurology Service, Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, United States of America; Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, United States of America.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Cooper
authors.affiliation: Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center, Nashville, TN, United States of America; Vanderbilt-Ingram Cancer Center (VICC), Vanderbilt University Medical Center, Nashville, TN, United States of America; Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN, United States of America; Program in Chemical and Physical Biology, Vanderbilt University Medical Center, Nashville, TN, United States of America; Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, United States of America.
authors.forename: H Charles
authors.initials: HC
authors.lastname: Manning
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000494:pharmacology; D051381:Rats; D018079:Receptors, GABA / Q000378:metabolism*; D012680:Sensitivity and Specificity; D046888:Tissue Array Analysis / Q000379:methods
chemical_list: D000083:Acetanilides; C538798:N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C499229:TSPO protein, human