Non-invasive PET Imaging of PARP1 Expression in Glioblastoma Models

Brandon Carney; Giuseppe Carlucci; Beatriz Salinas; Valentina Di Gialleonardo; Susanne Kossatz; Axel Vansteene; Valerie A. Longo; Alexander Bolaender; Gabriela Chiosis; Kayvan R. Keshari; Wolfgang A. Weber; Thomas Reiner

doi:10.1007/s11307-015-0904-y

Non-invasive PET Imaging of PARP1 Expression in Glioblastoma Models

Brandon Carney, Giuseppe Carlucci, Beatriz Salinas, Valentina Di Gialleonardo, Susanne Kossatz, Axel Vansteene, Valerie A. Longo, Alexander Bolaender, Gabriela Chiosis, Kayvan R. Keshari, Wolfgang A. Weber, Thomas Reiner

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

72 Scopus citations

Abstract

Purpose: The current study presents [¹⁸F]PARPi as imaging agent for PARP1 expression. Procedures: [¹⁸F]PARPi was generated by conjugating a 2H-phthalazin-1-one scaffold to 4-[¹⁸F]fluorobenzoic acid. Biochemical assays, optical in vivo competition, biodistribution analysis, positron emission tomography (PET)/X-ray computed tomography, and PET/magnetic resonance imaging studies were performed in subcutaneous and orthotopic mouse models of glioblastoma. Results: [¹⁸F]PARPi shows suitable pharmacokinetic properties for brain tumor imaging (IC₅₀ = 2.8 ± 1.1 nM; logP_CHI = 2.15 ± 0.41; plasma-free fraction = 63.9 ± 12.6 %) and accumulates selectively in orthotopic brain tumor tissue. Tracer accumulation in subcutaneous brain tumors was 1.82 ± 0.21 %ID/g, whereas in healthy brain, the uptake was only 0.04 ± 0.01 %ID/g. Conclusions: [¹⁸F]PARPi is a selective PARP1 imaging agent that can be used to visualize glioblastoma in xenograft and orthotopic mouse models with high precision and good signal/noise ratios. It offers new opportunities to non-invasively image tumor growth and monitor interventions.

Original language	English
Pages (from-to)	386-392
Number of pages	7
Journal	Molecular Imaging and Biology
Volume	18
Issue number	3
DOIs	https://doi.org/10.1007/s11307-015-0904-y
State	Published - Jun 2016
Externally published	Yes

Keywords

Glioblastoma
Imaging
Orthotopic
PARP1
PET

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s11307-015-0904-y

Cite this

@article{f9f58d686f4b49c0aa934011ce7e33c3,

title = "Non-invasive PET Imaging of PARP1 Expression in Glioblastoma Models",

abstract = "Purpose: The current study presents [18F]PARPi as imaging agent for PARP1 expression. Procedures: [18F]PARPi was generated by conjugating a 2H-phthalazin-1-one scaffold to 4-[18F]fluorobenzoic acid. Biochemical assays, optical in vivo competition, biodistribution analysis, positron emission tomography (PET)/X-ray computed tomography, and PET/magnetic resonance imaging studies were performed in subcutaneous and orthotopic mouse models of glioblastoma. Results: [18F]PARPi shows suitable pharmacokinetic properties for brain tumor imaging (IC50 = 2.8 ± 1.1 nM; logPCHI = 2.15 ± 0.41; plasma-free fraction = 63.9 ± 12.6 %) and accumulates selectively in orthotopic brain tumor tissue. Tracer accumulation in subcutaneous brain tumors was 1.82 ± 0.21 %ID/g, whereas in healthy brain, the uptake was only 0.04 ± 0.01 %ID/g. Conclusions: [18F]PARPi is a selective PARP1 imaging agent that can be used to visualize glioblastoma in xenograft and orthotopic mouse models with high precision and good signal/noise ratios. It offers new opportunities to non-invasively image tumor growth and monitor interventions.",

keywords = "Glioblastoma, Imaging, Orthotopic, PARP1, PET",

author = "Brandon Carney and Giuseppe Carlucci and Beatriz Salinas and {Di Gialleonardo}, Valentina and Susanne Kossatz and Axel Vansteene and Longo, {Valerie A.} and Alexander Bolaender and Gabriela Chiosis and Keshari, {Kayvan R.} and Weber, {Wolfgang A.} and Thomas Reiner",

note = "Publisher Copyright: {\textcopyright} 2015, World Molecular Imaging Society.",

year = "2016",

month = jun,

doi = "10.1007/s11307-015-0904-y",

language = "English",

volume = "18",

pages = "386--392",

journal = "Molecular Imaging and Biology",

issn = "1536-1632",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "3",

}

TY - JOUR

T1 - Non-invasive PET Imaging of PARP1 Expression in Glioblastoma Models

AU - Carney, Brandon

AU - Carlucci, Giuseppe

AU - Salinas, Beatriz

AU - Di Gialleonardo, Valentina

AU - Kossatz, Susanne

AU - Vansteene, Axel

AU - Longo, Valerie A.

AU - Bolaender, Alexander

AU - Chiosis, Gabriela

AU - Keshari, Kayvan R.

AU - Weber, Wolfgang A.

AU - Reiner, Thomas

PY - 2016/6

Y1 - 2016/6

N2 - Purpose: The current study presents [18F]PARPi as imaging agent for PARP1 expression. Procedures: [18F]PARPi was generated by conjugating a 2H-phthalazin-1-one scaffold to 4-[18F]fluorobenzoic acid. Biochemical assays, optical in vivo competition, biodistribution analysis, positron emission tomography (PET)/X-ray computed tomography, and PET/magnetic resonance imaging studies were performed in subcutaneous and orthotopic mouse models of glioblastoma. Results: [18F]PARPi shows suitable pharmacokinetic properties for brain tumor imaging (IC50 = 2.8 ± 1.1 nM; logPCHI = 2.15 ± 0.41; plasma-free fraction = 63.9 ± 12.6 %) and accumulates selectively in orthotopic brain tumor tissue. Tracer accumulation in subcutaneous brain tumors was 1.82 ± 0.21 %ID/g, whereas in healthy brain, the uptake was only 0.04 ± 0.01 %ID/g. Conclusions: [18F]PARPi is a selective PARP1 imaging agent that can be used to visualize glioblastoma in xenograft and orthotopic mouse models with high precision and good signal/noise ratios. It offers new opportunities to non-invasively image tumor growth and monitor interventions.

AB - Purpose: The current study presents [18F]PARPi as imaging agent for PARP1 expression. Procedures: [18F]PARPi was generated by conjugating a 2H-phthalazin-1-one scaffold to 4-[18F]fluorobenzoic acid. Biochemical assays, optical in vivo competition, biodistribution analysis, positron emission tomography (PET)/X-ray computed tomography, and PET/magnetic resonance imaging studies were performed in subcutaneous and orthotopic mouse models of glioblastoma. Results: [18F]PARPi shows suitable pharmacokinetic properties for brain tumor imaging (IC50 = 2.8 ± 1.1 nM; logPCHI = 2.15 ± 0.41; plasma-free fraction = 63.9 ± 12.6 %) and accumulates selectively in orthotopic brain tumor tissue. Tracer accumulation in subcutaneous brain tumors was 1.82 ± 0.21 %ID/g, whereas in healthy brain, the uptake was only 0.04 ± 0.01 %ID/g. Conclusions: [18F]PARPi is a selective PARP1 imaging agent that can be used to visualize glioblastoma in xenograft and orthotopic mouse models with high precision and good signal/noise ratios. It offers new opportunities to non-invasively image tumor growth and monitor interventions.

KW - Glioblastoma

KW - Imaging

KW - Orthotopic

KW - PARP1

KW - PET

UR - http://www.scopus.com/inward/record.url?scp=84944929454&partnerID=8YFLogxK

U2 - 10.1007/s11307-015-0904-y

DO - 10.1007/s11307-015-0904-y

M3 - Article

C2 - 26493053

AN - SCOPUS:84944929454

SN - 1536-1632

VL - 18

SP - 386

EP - 392

JO - Molecular Imaging and Biology

JF - Molecular Imaging and Biology

IS - 3

ER -

Non-invasive PET Imaging of PARP1 Expression in Glioblastoma Models

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this