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 ([18F]VUIIS1018A) by targeting translocator protein (TSPO), an imaging biomarker for glioma. The purpose of this preclinical stud...
| Publicado en: | Molecular Imaging & Biology Vol. 21; no. 1; pp. 113 - 122 |
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| Autores principales: | , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Springer Nature
Feb2019
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=134786698&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 134786698 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 15361632 KJU jtl: Molecular Imaging & Biology issn: 15361632 maglogo: N pubinfo: dt: Feb2019 vid: 21 iid: 1 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 134786698 134786698 NLM29869061 134786698 10.1007/s11307-018-1198-7 NLM29869061 134786698 ppf: 113 ppct: 9 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: 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. aug: au: Tang, Dewei Li, Jun Nickels, Michael L. Huang, Gang Cohen, Allison S. Manning, H. Charles affil: Center for Molecular Imaging, Shanghai University of Medicine & Health Sciences, Shanghai, China sug: subj: Heterocyclic Compounds Pharmacokinetics Glioma Diagnosis Tomography, Emission-Computed Methods Fluorine Radioisotopes Pharmacokinetics Brain Neoplasms Diagnosis Carrier Proteins Brain Neoplasms Pathology Disease Progression Magnetic Resonance Imaging Animal Studies Male Glioma Pathology Ligands Receptors, Cell Surface Metabolism Drug Evaluation, Preclinical Tumor Cells, Cultured Rats Carrier Proteins Metabolism Validation Studies Comparative Studies Evaluation Research Multicenter Studies Male ab: 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 ([18F]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 [19F]VUIIS1018A and the precursor for radiosynthesis of [18F]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 [18F]VUIIS1008 and [18F]DPA-714, the novel tracer [18F]VUIIS1018A demonstrated higher binding affinity and BPND. Pretreatment with the cold analog [19F]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 [18F]DPA-714 and [18F]VUIIS1008.Conclusions: These studies illustrate that [18F]VUIIS1018A can serve as a promising TSPO PET tracer for glioma imaging and potentially imaging of other solid tumors. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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