Four 4-phthalimide derivatives of N-(3-chlorophenyl)-2-picolinamide were synthesized as potential ligands for the PET imaging of mGlu4 in the brain. Of these compounds, N-(3-chloro-4-(4-fluoro-1,3-dioxoisoindolin-2-yl)phenyl)-2-picolinamide (3, KALB001) exhibited improved binding affinity (IC50 = 5.1 nM) compared with ML128 (1) and was subsequently labeled with (18)F. When finally formulated in 0.1 M citrate buffer (pH 4) with 10% ethanol, the specific activity of [(18)F]3 at the end of synthesis (EOS) was 233.5 ± 177.8 GBq/μmol (n = 4).
Jacob Hooker has been awarded a prestigious grant from the Brain & Behavior Research Foundation. The grant will support work by his group exploring the underpinnings of such disease.
International Innovation talks to the Martinos Center's Anna-Liisa Brownell about her work with PET imaging and the insights it provides into neurodegenerative disease
Evidence from human post mortem, in vivo and animal model studies implicates the neuroimmune system and activated microglia in the pathology of amyotrophic lateral sclerosis. The study aim was to further evaluate in vivo neuroinflammation in individuals with amyotrophic lateral sclerosis using [(11)C]-PBR28 positron emission tomography. Ten patients with amyotrophic lateral sclerosis (seven males, three females, 38-68 years) and ten age- and [(11)C]-PBR28 binding affinity-matched healthy volunteers (six males, four females, 33-65 years) completed a positron emission tomography scan.
Non-invasive positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are techniques used to quantify molecular interactions, biological processes and protein concentration and distribution. In the central nervous system, these molecular imaging techniques can provide critical insights into neurotransmitter receptors and their occupancy by neurotransmitters or drugs.
Simultaneous PET-MR is a novel and promising imaging modality that is generating substantial interest in the medical imaging community, while offering many challenges and opportunities. In this study, we investigated whether MR surface coils need to be accounted for in PET attenuation correction. Furthermore, we integrated motion correction, attenuation correction, and point spread function modeling into a single PET reconstruction framework. We applied our reconstruction framework to in vivo animal and patient PET-MR studies.
PURPOSE: Estrogen receptor (ER) targeting is key in management of receptor-positive breast cancer. Currently, there are no methods to optimize anti-ER therapy dosing. This study assesses the use of 16α-(18)F-fluoroestradiol ((18)F-FES) PET for fulvestrant dose optimization in a preclinical ER(+) breast cancer model.
The Hooker Research Group's Nicole Zürcher and colleagues published the study this week. The findings could also have a significant impact on future drug development.
Many studies have reported long-term modulation of metabotropic glutamate receptor 5 (mGluR5) by inflammatory processes and a pharmacological modulation of mGluR5 is known to regulate anxiety level. However, it is not known if non-pharmacological modulation of mGluR5 by inflammation impaired the unconditional level of anxiety. In this study, we investigated this relation in LPS prenatal immune challenge (120μg/kg, 3x i.p. injection in late gestation), a developmental model of neuroinflammation in which some studies have reported hypo-anxious phenotype.
