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J Nucl Med. 2017 Jun;58(6):982-988. doi: 10.2967/jnumed.116.188052. Epub 2017 Feb 23.

PET Imaging Evaluation of Four σ1 Radiotracers in Nonhuman Primates.

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PET Center, Department of Radiology and Biomedical Imaging, Yale University, New Haven, Connecticut.
Ministry of Education Key Laboratory of Radiopharmaceuticals, College of Chemistry, Beijing Normal University, Beijing, China.
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Leipzig, Germany; and.
Department of Pharmaceutical and Medicinal Chemistry, Westfälische Wilhelms-Universität Münster, Münster, Germany.
PET Center, Department of Radiology and Biomedical Imaging, Yale University, New Haven, Connecticut


The σ1 receptors (S1Rs) are implicated in a variety of diseases including Alzheimer disease and cancer. Previous PET S1R radiotracers are characterized by slow kinetics or off-target binding that impedes their use in humans. Here, we report the first PET imaging evaluation in rhesus monkeys of 4 18F-labeled spirocyclic piperidine-based PET radiotracers (18F-1 to 18F-4). Methods: Baseline scans for the 4 radiotracers were obtained on an adult male rhesus monkey. Blocking scans were obtained with the S1R-selective agonist SA4503 to assess binding specificity of 18F-2 and 18F-4 Arterial input functions were measured, and binding parameters were determined with kinetic modeling analysis. Results: In the rhesus brain, all 4 radiotracers showed high and fast uptake. Tissue activity washout was rapid for 18F-2 and 18F-4, and much slower for 18F-1 and 18F-3, in line with their respective in vitro S1R-binding affinities. Both the 1-tissue-compartment and multilinear analysis-1 kinetic models provided good fits of time-activity curves and reliable estimates of distribution volume. Regional distribution volume values were highest in the cingulate cortex and lowest in the thalamus for all radiotracers. 18F-4 showed greater differential uptake across brain regions and 3-fold-higher binding potential than 18F-2 SA4503 at the dose of 0.5 mg/kg blocked approximately 85% (18F-2) and 95% (18F-4) of radiotracer binding. Conclusion: Tracers 18F-2 and 18F-4 displayed high brain uptake and fast tissue kinetics, with 18F-4 having higher specific binding signals than 18F-2 in the same monkey. Taken together, these data indicate that both 18F-2 and 18F-4 possess the requisite kinetic and imaging properties as viable PET tracers for imaging S1R in the human brain.


18F; PET; radioligand; rhesus monkey; sigma-1 receptor

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