Synapse - Non-invasive PET imaging of PARP1 expression in glioblastoma models

Non-invasive PET imaging of PARP1 expression in glioblastoma models Journal Article

Authors:	Carney, B.; Carlucci, G.; Salinas, B.; Di Gialleonardo, V.; Kossatz, S.; Vansteene, A.; Longo, V. A.; Bolaender, A.; Chiosis, G.; Keshari, K. R.; Weber, W. A.; Reiner, T.
Article Title:	Non-invasive PET imaging of PARP1 expression in glioblastoma models
Abstract:	The current study presents [F-18]PARPi as imaging agent for PARP1 expression. [F-18]PARPi was generated by conjugating a 2H-phthalazin-1-one scaffold to 4-[F-18]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. [F-18]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. [F-18]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:	dna; glioblastoma; imaging; in-vivo; pet; olaparib; orthotopic; breast-cancer; acid; inhibition; f-18; single-cell; polymerase-1; parp1
Journal Title:	Molecular Imaging and Biology
Volume:	18
Issue:	3
ISSN:	1536-1632
Publisher:	Springer
Date Published:	2016-06-01
Start Page:	386
End Page:	392
Language:	English
ACCESSION:	WOS:000376623600010
DOI:	10.1007/s11307-015-0904-y
PROVIDER:	wos
PMCID:	PMC4841747
PUBMED:	26493053
Notes:	Article -- Source: Wos