title: In vivo evaluation of IGF1R/IR PET ligand [18F]BMS-754807 in rodents.
abstract: In vivo evaluation of [18F]BMS-754807 binding in mice and rats using microPET and biodistribution methods is described herein. The radioligand shows consistent binding characteristics, in vivo, in both species. Early time frames of the microPET images and time activity curves of brain indicate poor penetration of the tracer across the blood brain barrier (BBB) in both species. However, microPET experiments in mice and rats show high binding of the radioligand outside the brain to heart, pancreas and muscle, the organs known for higher expression of IGF1R/1R. Biodistribution analysis 2h after injection of [18F]BMS-754807 in rats show negligible [18F]defluorination as reflected by the low bone uptake and clearance from blood. Overall, the data indicate that [18F]BMS-754807 can potentially be a radiotracer for the quantification of IGF1R/IR outside the brain using PET.
authors.affiliation: Department of Psychiatry, Columbia University Medical Center, New York, USA; Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, USA.
authors.forename: Jaya
authors.initials: J
authors.lastname: Prabhakaran
authors.affiliation: Feinstein Institute for Medical Research, Hofstra North Shore - LIJ School of Medicine, Manhasset, NY, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Dewey
authors.affiliation: Institute of Imaging Science, Department of Radiology, Vanderbilt University, USA; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: McClure
authors.affiliation: Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, USA.
authors.forename: Norman R
authors.initials: NR
authors.lastname: Simpson
authors.affiliation: Institute of Imaging Science, Department of Radiology, Vanderbilt University, USA.
authors.forename: Mohammed N
authors.initials: MN
authors.lastname: Tantawy
authors.affiliation: Department of Psychiatry, Columbia University Medical Center, New York, USA; Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, USA.
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
authors.affiliation: Institute of Imaging Science, Department of Radiology, Vanderbilt University, USA; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
authors.forename: Wellington
authors.initials: W
authors.lastname: Pham
authors.affiliation: Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, USA. Electronic address: kumardi@nyspi.columbia.edu.
authors.forename: J S Dileep
authors.initials: JSD
authors.lastname: Kumar
mesh_terms: D000818:Animals; D005462:Fluorine Radioisotopes / Q000378:metabolism; D064593:Heterografts; D006801:Humans; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D011720:Pyrazoles / Q000493:pharmacokinetics*; D011869:Radioligand Assay; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism*; D014227:Triazines / Q000493:pharmacokinetics*
chemical_list: C545990:BMS 754807; D005462:Fluorine Radioisotopes; D011720:Pyrazoles; D014227:Triazines; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin
keywords: IGF1R; IR; Insulin; MicroPET; Radiotracer