Non-invasive PET Imaging of PARP1 Expression in Glioblastoma Models.
The current study presents [(18)F]PARPi as imaging agent for PARP1 expression.



[(18)F]PARPi was generated by conjugating a 2H-phthalazin-1-one scaffold to 4-[(18)F]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.



[(18)F]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.



[(18)F]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.
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York City, NY, 10065, USA.|Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York City, NY, 10018, USA.
Brandon
B
Carney
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York City, NY, 10065, USA.
Giuseppe
G
Carlucci
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York City, NY, 10065, USA.
Beatriz
B
Salinas
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York City, NY, 10065, USA.
Valentina
V
Di Gialleonardo
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York City, NY, 10065, USA.
Susanne
S
Kossatz
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York City, NY, 10065, USA.
Axel
A
Vansteene
Small-Animal Imaging Core Facility, Memorial Sloan Kettering Cancer Center, New York City, NY, 10065, USA.
Valerie A
VA
Longo
Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York City, NY, 10065, USA.
Alexander
A
Bolaender
Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York City, NY, 10065, USA.
Gabriela
G
Chiosis
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York City, NY, 10065, USA.|Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York City, NY, 10065, USA.|Weill Cornell Medical College, New York City, NY, 10065, USA.
Kayvan R
KR
Keshari
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York City, NY, 10065, USA.|Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York City, NY, 10065, USA.|Weill Cornell Medical College, New York City, NY, 10065, USA.
Wolfgang A
WA
Weber
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York City, NY, 10065, USA. reinert@mskcc.org.|Weill Cornell Medical College, New York City, NY, 10065, USA. reinert@mskcc.org.
Thomas
T
Reiner
D000818:Animals; D001345:Autoradiography; D001798:Blood Proteins / Q000378:metabolism; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005462:Fluorine Radioisotopes; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000201:enzymology* / Q000473:pathology; D006207:Half-Life; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D014018:Tissue Distribution / Q000187:drug effects; D014057:Tomography, X-Ray Computed
D001798:Blood Proteins; D005462:Fluorine Radioisotopes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases
Glioblastoma; Imaging; Orthotopic; PARP1; PET