Preclinical Imaging Evaluation of Novel TSPO-PET Ligand 2-(5,7-Diethyl-2-(4-(2-[18F]fluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide ([18F]VUIIS1008) in Glioma

Dewei Tang; Michael L. Nickels; M. Noor Tantawy; Jason R. Buck; H. Charles Manning

doi:10.1007/s11307-014-0743-2

Preclinical Imaging Evaluation of Novel TSPO-PET Ligand 2-(5,7-Diethyl-2-(4-(2-[¹⁸F]fluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide ([¹⁸F]VUIIS1008) in Glioma

Dewei Tang, Michael L. Nickels, M. Noor Tantawy, Jason R. Buck, H. Charles Manning

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

Abstract

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, [¹⁸F]VUIIS1008, in healthy mice and glioma-bearing rats.

Procedures: Dynamic PET data were acquired simultaneously with [¹⁸F]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: [¹⁸F]VUIIS1008 exhibited rapid uptake in TSPO-rich organs. PET ligand uptake was displaceable with non-radioactive VUIIS1008 or PBR06 in mice. Tumor accumulation of [¹⁸F]VUIIS1008 was blocked by pretreatment with VUIIS1008 in rats. [¹⁸F]VUIIS1008 exhibited improved tumor-to-background ratio and higher binding potential in tumors compared to a structurally similar pyrazolopyrimidine TSPO ligand, [¹⁸F]DPA-714.

Conclusions: The PET ligand [¹⁸F]VUIIS1008 exhibits promising characteristics as a tracer for imaging glioma. Further translational studies appear warranted.

Original language	English (US)
Pages (from-to)	813-820
Number of pages	8
Journal	Molecular Imaging and Biology
Volume	16
Issue number	6
DOIs	https://doi.org/10.1007/s11307-014-0743-2
State	Published - Nov 18 2014
Externally published	Yes

Keywords

Cancer imaging
DPA-714
Glioma
PET
TSPO
VUIIS1008

ASJC Scopus subject areas

Oncology
Radiology Nuclear Medicine and imaging
Cancer Research

Access to Document

10.1007/s11307-014-0743-2

Cite this

Preclinical Imaging Evaluation of Novel TSPO-PET Ligand 2-(5,7-Diethyl-2-(4-(2-[¹⁸F]fluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide ([¹⁸F]VUIIS1008) in Glioma. / Tang, Dewei; Nickels, Michael L.; Tantawy, M. Noor et al.
In: Molecular Imaging and Biology, Vol. 16, No. 6, 18.11.2014, p. 813-820.

Research output: Contribution to journal › Article › peer-review

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title = "Preclinical Imaging Evaluation of Novel TSPO-PET Ligand 2-(5,7-Diethyl-2-(4-(2-[18F]fluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide ([18F]VUIIS1008) in Glioma",

abstract = "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, [18F]VUIIS1008, in healthy mice and glioma-bearing rats.Procedures: Dynamic PET data were acquired simultaneously with [18F]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: [18F]VUIIS1008 exhibited rapid uptake in TSPO-rich organs. PET ligand uptake was displaceable with non-radioactive VUIIS1008 or PBR06 in mice. Tumor accumulation of [18F]VUIIS1008 was blocked by pretreatment with VUIIS1008 in rats. [18F]VUIIS1008 exhibited improved tumor-to-background ratio and higher binding potential in tumors compared to a structurally similar pyrazolopyrimidine TSPO ligand, [18F]DPA-714.Conclusions: The PET ligand [18F]VUIIS1008 exhibits promising characteristics as a tracer for imaging glioma. Further translational studies appear warranted.",

keywords = "Cancer imaging, DPA-714, Glioma, PET, TSPO, VUIIS1008",

author = "Dewei Tang and Nickels, {Michael L.} and Tantawy, {M. Noor} and Buck, {Jason R.} and Manning, {H. Charles}",

note = "Publisher Copyright: {\textcopyright} 2014, World Molecular Imaging Society.",

year = "2014",

month = nov,

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doi = "10.1007/s11307-014-0743-2",

language = "English (US)",

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AU - Tang, Dewei

AU - Nickels, Michael L.

AU - Tantawy, M. Noor

AU - Buck, Jason R.

AU - Manning, H. Charles

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N2 - 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, [18F]VUIIS1008, in healthy mice and glioma-bearing rats.Procedures: Dynamic PET data were acquired simultaneously with [18F]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: [18F]VUIIS1008 exhibited rapid uptake in TSPO-rich organs. PET ligand uptake was displaceable with non-radioactive VUIIS1008 or PBR06 in mice. Tumor accumulation of [18F]VUIIS1008 was blocked by pretreatment with VUIIS1008 in rats. [18F]VUIIS1008 exhibited improved tumor-to-background ratio and higher binding potential in tumors compared to a structurally similar pyrazolopyrimidine TSPO ligand, [18F]DPA-714.Conclusions: The PET ligand [18F]VUIIS1008 exhibits promising characteristics as a tracer for imaging glioma. Further translational studies appear warranted.

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, [18F]VUIIS1008, in healthy mice and glioma-bearing rats.Procedures: Dynamic PET data were acquired simultaneously with [18F]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: [18F]VUIIS1008 exhibited rapid uptake in TSPO-rich organs. PET ligand uptake was displaceable with non-radioactive VUIIS1008 or PBR06 in mice. Tumor accumulation of [18F]VUIIS1008 was blocked by pretreatment with VUIIS1008 in rats. [18F]VUIIS1008 exhibited improved tumor-to-background ratio and higher binding potential in tumors compared to a structurally similar pyrazolopyrimidine TSPO ligand, [18F]DPA-714.Conclusions: The PET ligand [18F]VUIIS1008 exhibits promising characteristics as a tracer for imaging glioma. Further translational studies appear warranted.

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