Preclinical imaging evaluation of novel TSPO-PET ligand 2-(5,7-Diethyl-2-(4-(2-[(18)F]fluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide ([ (18)F]VUIIS1008) in glioma.

Purpose: Translocator protein (TSPO) concentrations are elevated in glioma, suggesting a role for TSPO positron emission tomography (PET) imaging in this setting. In preclinical PET studies, we evaluated a novel, high-affinity TSPO PET ligand, [(18)F]VUIIS1008, in healthy mice and glioma-bearing rat...

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Publicado en:Molecular Imaging & Biology Vol. 16; no. 6; pp. 813 - 821
Autores principales: Tang, Dewei, Nickels, Michael L, Tantawy, M Noor, Buck, Jason R, Manning, H Charles
Formato: research Journal Article
Publicado: Springer Nature Dec2014
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Dec2014
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s11307-014-0743-2
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        atl: Preclinical imaging evaluation of novel TSPO-PET ligand 2-(5,7-Diethyl-2-(4-(2-[(18)F]fluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide ([ (18)F]VUIIS1008) in glioma.
      aug:
        au:
          Tang, Dewei
          Nickels, Michael L
          Tantawy, M Noor
          Buck, Jason R
          Manning, H Charles
      sug:
        subj:
          Brain Neoplasms Metabolism
          Carrier Proteins Metabolism
          Fluorine Radioisotopes Diagnostic Use
          Glioma Metabolism
          Heterocyclic Compounds Diagnostic Use
          Receptors, Cell Surface Metabolism
          Tomography, Emission-Computed Methods
          Animal Studies
          Brain Neoplasms Pathology
          Brain Neoplasms Radiography
          Fluorine Radioisotopes Pharmacokinetics
          Glioma Pathology
          Glioma Radiography
          Heterocyclic Compounds Pharmacokinetics
          Ligands
          Mice
          Rats
      ab: Purpose: Translocator protein (TSPO) concentrations are elevated in glioma, suggesting a role for TSPO positron emission tomography (PET) imaging in this setting. In preclinical PET studies, we evaluated a novel, high-affinity TSPO PET ligand, [(18)F]VUIIS1008, in healthy mice and glioma-bearing rats.Procedures: Dynamic PET data were acquired simultaneously with [(18)F]VUIIS1008 injection, with binding reversibility and specificity evaluated in vivo by non-radioactive ligand displacement or blocking. Compartmental analysis of PET data was performed using metabolite-corrected arterial input functions. Imaging was validated with histology and immunohistochemistry.Results: [(18)F]VUIIS1008 exhibited rapid uptake in TSPO-rich organs. PET ligand uptake was displaceable with non-radioactive VUIIS1008 or PBR06 in mice. Tumor accumulation of [(18)F]VUIIS1008 was blocked by pretreatment with VUIIS1008 in rats. [(18)F]VUIIS1008 exhibited improved tumor-to-background ratio and higher binding potential in tumors compared to a structurally similar pyrazolopyrimidine TSPO ligand, [(18)F]DPA-714.Conclusions: The PET ligand [(18)F]VUIIS1008 exhibits promising characteristics as a tracer for imaging glioma. Further translational studies appear warranted.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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