Nasal neuron PET imaging quantifies neuron generation and degeneration
Genevieve C. Van de Bittner, … , Mark W. Albers, Jacob M. Hooker
Genevieve C. Van de Bittner, … , Mark W. Albers, Jacob M. Hooker
Published January 23, 2017
Citation Information: J Clin Invest. 2017;127(2):681-694. https://doi.org/10.1172/JCI89162.
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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

Genevieve C. Van de Bittner, Misha M. Riley, Luxiang Cao, Janina Ehses, Scott P. Herrick, Emily L. Ricq, Hsiao-Ying Wey, Michael J. O’Neill, Zeshan Ahmed, Tracey K. Murray, Jaclyn E. Smith, Changning Wang, Frederick A. Schroeder, Mark W. Albers, Jacob M. Hooker

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Figure 1

[11C]GV1-57 localizes to the OE and exhibits saturable binding.

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[11C]GV1-57 localizes to the OE and exhibits saturable binding. (A) Repr...
(A) Representative coregistered CT and [11C]GV1-57 PET images (SUV, NIH+white, 3–45 minutes) following treatment with [11C]GV1-57 (0.97 ± 0.097 mCi per animal). [11C]GV1-57 uptake is specific to the OE, which is circled in red in sagittal, transverse, and coronal views (left to right). (B) Representative [11C]GV1-57 PET images (SUV, NIH+white, 3–45 minutes) following pretreatment with nonradiolabeled GV1-57 (i.v., 16 mg/kg) 5 minutes prior to administration of [11C]GV1-57 (0.89 ± 0.032 mCi per animal). (C) Binding potential (BP) quantification of [11C]GV1-57 uptake in the OE of rats treated as described in A and B. BP was determined using a Logan analysis (Supplemental Figure 2). Error bars are ± SEM; n = 3 per group. ***P < 0.005 using a 2-tailed Student’s t test. (D) Averaged time-activity curves from rats treated as described in A and B. Error bars are ± SEM; n = 3 per group. %ID/cc, percent injected dose per cubic centimeter. (E) In vivo IC50 curve for [11C]GV1-57 (IC50 = 1.5 mg/kg, ~20 μM); rats coadministered with [11C]GV1-57 (0.52 ± 0.025 mCi) and increasing doses of nonradiolabeled GV1-57 (i.v., 0–4 mg/kg). Graph includes the [11C]GV1-57 BP obtained in C for animals pretreated with 16 mg/kg nonradiolabeled GV1-57.