title: Nasal neuron PET imaging quantifies neuron generation and degeneration.
abstract: Olfactory dysfunction is broadly associated with neurodevelopmental and neurodegenerative diseases and predicts increased mortality rates in healthy individuals. Conventional measurements of olfactory health assess odor processing pathways within the brain and provide a limited understanding of primary odor detection. Quantification of the olfactory sensory neurons (OSNs), which detect odors within the nasal cavity, would provide insight into the etiology of olfactory dysfunction associated with disease and mortality. Notably, OSNs are continually replenished by adult neurogenesis in mammals, including humans, so OSN measurements are primed to provide specialized insights into neurological disease. Here, we have evaluated a PET radiotracer, [11C]GV1-57, that specifically binds mature OSNs and quantifies the mature OSN population in vivo. [11C]GV1-57 monitored native OSN population dynamics in rodents, detecting OSN generation during postnatal development and aging-associated neurodegeneration. [11C]GV1-57 additionally measured rates of neuron regeneration after acute injury and early-stage OSN deficits in a rodent tauopathy model of neurodegenerative disease. Preliminary assessment in nonhuman primates suggested maintained uptake and saturable binding of [18F]GV1-57 in primate nasal epithelium, supporting its translational potential. Future applications for GV1-57 include monitoring additional diseases or conditions associated with olfactory dysregulation, including cognitive decline, as well as monitoring effects of neuroregenerative or neuroprotective therapeutics.
authors.forename: Genevieve C
authors.initials: GC
authors.lastname: Van de Bittner
authors.forename: Misha M
authors.initials: MM
authors.lastname: Riley
authors.forename: Luxiang
authors.initials: L
authors.lastname: Cao
authors.forename: Janina
authors.initials: J
authors.lastname: Ehses
authors.forename: Scott P
authors.initials: SP
authors.lastname: Herrick
authors.forename: Emily L
authors.initials: EL
authors.lastname: Ricq
authors.forename: Hsiao-Ying
authors.initials: HY
authors.lastname: Wey
authors.forename: Michael J
authors.initials: MJ
authors.lastname: O'Neill
authors.forename: Zeshan
authors.initials: Z
authors.lastname: Ahmed
authors.forename: Tracey K
authors.initials: TK
authors.lastname: Murray
authors.forename: Jaclyn E
authors.initials: JE
authors.lastname: Smith
authors.forename: Changning
authors.initials: C
authors.lastname: Wang
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Schroeder
authors.forename: Mark W
authors.initials: MW
authors.lastname: Albers
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Hooker
mesh_terms: D000375:Aging; D000818:Animals; D008297:Male; D000857:Olfaction Disorders / Q000000981:diagnostic imaging* / Q000503:physiopathology; D009832:Olfactory Nerve / Q000000981:diagnostic imaging* / Q000503:physiopathology; D009833:Olfactory Pathways / Q000000981:diagnostic imaging* / Q000503:physiopathology; D049268:Positron-Emission Tomography / Q000379:methods*; D011849:Radioactive Tracers; D051381:Rats; D017207:Rats, Sprague-Dawley; D024801:Tauopathies / Q000000981:diagnostic imaging* / Q000503:physiopathology
chemical_list: D011849:Radioactive Tracers