Preclinical Evaluation of a Novel TSPO PET Ligand 2-(7-Butyl-2-(4-(2-[18F]Fluoroethoxy)phenyl)-5-Methylpyrazolo[1,5-a]Pyrimidin-3-yl)-N,N-Diethylacetamide (18F-VUIIS1018A) to Image Glioma

Purpose There is an urgent need for the development of novel positron emission tomography (PET) tracers for glioma imaging. In this study, we developed a novel PET probe ([ 18 F]VUIIS1018A) by targeting translocator protein (TSPO), an imaging biomarker for glioma. The purpose of this preclinical stu...

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Bibliographic Details
Published in:Molecular imaging and biology 2019-02, Vol.21 (1), p.113-121
Main Authors: Tang, Dewei, Li, Jun, Nickels, Michael L., Huang, Gang, Cohen, Allison S., Manning, H. Charles
Format: Article
Language:English
Subjects:
Affinity
Animals
Binding
Biomarkers
Blocking
Brain
Brain Neoplasms - diagnosis
Brain Neoplasms - pathology
Brain tumors
Carrier Proteins - agonists
Carrier Proteins - metabolism
Disease Progression
Drug Evaluation, Preclinical
Emission analysis
Evaluation
Fluorine isotopes
Fluorine Radioisotopes - pharmacokinetics
Glioma
Glioma - diagnosis
Glioma - pathology
Glioma cells
Imaging
Ligands
Magnetic Resonance Imaging
Male
Medical imaging
Medicine
Medicine & Public Health
Metabolites
Modelling
Neuroimaging
Pharmacokinetics
Pharmacology
Positron emission
Positron emission tomography
Positron-Emission Tomography - methods
Proteins
Pyrazoles - pharmacokinetics
Pyrimidines - pharmacokinetics
Radiology
Rats
Rats, Wistar
Receptors, GABA-A - metabolism
Research Article
Solid tumors
Studies
Tomography
Tracers
Tumor Cells, Cultured
Tumors
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Description
Summary:Purpose There is an urgent need for the development of novel positron emission tomography (PET) tracers for glioma imaging. In this study, we developed a novel PET probe ([ 18 F]VUIIS1018A) by targeting translocator protein (TSPO), an imaging biomarker for glioma. The purpose of this preclinical study was to evaluate this novel TSPO probe for glioma imaging. Procedures In this study, we synthesized [ 19 F]VUIIS1018A and the precursor for radiosynthesis of [ 18 F]VUIIS1018A. TSPO binding affinity was confirmed using a radioligand competitive binding assay in C6 glioma cell lysate. Further, dynamic imaging studies were performed in rats using a microPET system. These studies include displacement and blocking studies for ligand reversibility and specificity evaluation, and compartment modeling of PET data for pharmacokinetic parameter measurement using metabolite-corrected arterial input functions and PMOD. Results Compared to previously reported TSPO tracers including [ 18 F]VUIIS1008 and [ 18 F]DPA-714, the novel tracer [ 18 F]VUIIS1018A demonstrated higher binding affinity and BP ND . Pretreatment with the cold analog [ 19 F]VUIIS1018A could partially block tumor accumulation of this novel tracer. Further, compartment modeling of this novel tracer also exhibited a greater tumor-to-background ratio, a higher tumor binding potential and a lower brain binding potential when compared with other TSPO probes, such as [ 18 F]DPA-714 and [ 18 F]VUIIS1008. Conclusions These studies illustrate that [ 18 F]VUIIS1018A can serve as a promising TSPO PET tracer for glioma imaging and potentially imaging of other solid tumors.
ISSN:1536-1632
1860-2002
DOI:10.1007/s11307-018-1198-7