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5-HT2A Receptors in the feline brain: 123I-5-I-R91150 kinetics and the influence of ketamine measured with micro-SPECT

(2013) JOURNAL OF NUCLEAR MEDICINE. 54(8). p.1428-1433
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Abstract
Subanesthetic doses of ketamine can be used as a rapid-acting antidepressant in patients with treatment-resistant depression. Therefore, the brain kinetics of I-123-5-I-R91150 (4-amino-N-[1-[3-(4-fluorophenyl)propyl]-4-methylpiperidin-4-yl]-5-iodo-2-methoxy-benzamide) and the influence of ketamine on the postsynaptic serotonin-2A receptor (5-hydroxytryptamine-2A, or 5-HT2A) status were investigated in cats using micro-SPECT. Methods: This study was conducted on 6 cats using the radioligand I-123-5-I-R91150, a 5-HT2A receptor antagonist, as the imaging probe. Anesthesia was induced and maintained with a continuous-rate infusion of propofol (8.4 +/- 1.2 mg kg(-1) followed by 0.22 mg kg(-1) min(-1)) 75 min after tracer administration, and acquisition of the first image began 15 min after induction of anesthesia. After this first acquisition, propofol (0.22 mg kg(-1) min(-1)) was combined with ketamine (5 mg kg(-1) followed by 0.023 mg kg(-1) min(-1)), and the second acquisition began 15 min later. Semiquantification, with the cerebellum as a reference region, was performed to calculate the 5-HT2A receptor binding indices (parameter for available receptor density) in the frontal and temporal cortices. The binding indices were analyzed with Wilcoxon signed ranks statistics. Results: The addition of ketamine to the propofol continuous-rate infusion resulted in decreased binding indices in the right frontal cortex (1.25 +/- 0.22 vs. 1.45 +/- 0.16; P = 0.028), left frontal cortex (1.34 +/- 0.15 vs. 1.49 +/- 0.10; P = 0.028), right temporal cortex (1.30 +/- 0.17 vs. 1.45 +/- 0.09; P = 0.046), and left temporal cortex (1.41 +/- 0.20 vs. 1.52 +/-. 0.20; P = 0.046). Conclusion: This study showed that cats can be used as an animal model for studying alterations of the 5-HT2A receptor status with I-123-5-I-R91150 micro-SPECT. Furthermore, an interaction between ketamine and the 5-HT2A receptors resulting in decreased binding of I-123-5-I-R91150 in the frontal and temporal cortices was demonstrated. Whether the decreased radioligand binding resulted from a direct competition between ketamine and I-123-5-I-R91150 or from a decreased affinity of the 5-HT2A receptor caused by ketamine remains to be elucidated.
Keywords
ANTIDEPRESSANTS, HYPERTHYROIDISM, DOGS, LIGAND, DISORDERS, BINDING INDEX, MAJOR DEPRESSION, POSITRON-EMISSION-TOMOGRAPHY, SEROTONIN REUPTAKE INHIBITORS, CEREBRAL-BLOOD-FLOW, SPECT, 5-HT2A, brain, ketamine, cats

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Chicago
Waelbers, Tim, Ingeborgh Polis, Simon Vermeire, André Dobbeleir, Jos Eersels, Bart De Spiegeleer, Kurt Audenaert, Guido Slegers, and Kathelijne Peremans. 2013. “5-HT2A Receptors in the Feline Brain: 123I-5-I-R91150 Kinetics and the Influence of Ketamine Measured with micro-SPECT.” Journal of Nuclear Medicine 54 (8): 1428–1433.
APA
Waelbers, T., Polis, I., Vermeire, S., Dobbeleir, A., Eersels, J., De Spiegeleer, B., Audenaert, K., et al. (2013). 5-HT2A Receptors in the feline brain: 123I-5-I-R91150 kinetics and the influence of ketamine measured with micro-SPECT. JOURNAL OF NUCLEAR MEDICINE, 54(8), 1428–1433.
Vancouver
1.
Waelbers T, Polis I, Vermeire S, Dobbeleir A, Eersels J, De Spiegeleer B, et al. 5-HT2A Receptors in the feline brain: 123I-5-I-R91150 kinetics and the influence of ketamine measured with micro-SPECT. JOURNAL OF NUCLEAR MEDICINE. 2013;54(8):1428–33.
MLA
Waelbers, Tim, Ingeborgh Polis, Simon Vermeire, et al. “5-HT2A Receptors in the Feline Brain: 123I-5-I-R91150 Kinetics and the Influence of Ketamine Measured with micro-SPECT.” JOURNAL OF NUCLEAR MEDICINE 54.8 (2013): 1428–1433. Print.
@article{4180562,
  abstract     = {Subanesthetic doses of ketamine can be used as a rapid-acting antidepressant in patients with treatment-resistant depression. Therefore, the brain kinetics of I-123-5-I-R91150 (4-amino-N-[1-[3-(4-fluorophenyl)propyl]-4-methylpiperidin-4-yl]-5-iodo-2-methoxy-benzamide) and the influence of ketamine on the postsynaptic serotonin-2A receptor (5-hydroxytryptamine-2A, or 5-HT2A) status were investigated in cats using micro-SPECT. Methods: This study was conducted on 6 cats using the radioligand I-123-5-I-R91150, a 5-HT2A receptor antagonist, as the imaging probe. Anesthesia was induced and maintained with a continuous-rate infusion of propofol (8.4 +/- 1.2 mg kg(-1) followed by 0.22 mg kg(-1) min(-1)) 75 min after tracer administration, and acquisition of the first image began 15 min after induction of anesthesia. After this first acquisition, propofol (0.22 mg kg(-1) min(-1)) was combined with ketamine (5 mg kg(-1) followed by 0.023 mg kg(-1) min(-1)), and the second acquisition began 15 min later. Semiquantification, with the cerebellum as a reference region, was performed to calculate the 5-HT2A receptor binding indices (parameter for available receptor density) in the frontal and temporal cortices. The binding indices were analyzed with Wilcoxon signed ranks statistics. Results: The addition of ketamine to the propofol continuous-rate infusion resulted in decreased binding indices in the right frontal cortex (1.25 +/- 0.22 vs. 1.45 +/- 0.16; P = 0.028), left frontal cortex (1.34 +/- 0.15 vs. 1.49 +/- 0.10; P = 0.028), right temporal cortex (1.30 +/- 0.17 vs. 1.45 +/- 0.09; P = 0.046), and left temporal cortex (1.41 +/- 0.20 vs. 1.52 +/-. 0.20; P = 0.046). Conclusion: This study showed that cats can be used as an animal model for studying alterations of the 5-HT2A receptor status with I-123-5-I-R91150 micro-SPECT. Furthermore, an interaction between ketamine and the 5-HT2A receptors resulting in decreased binding of I-123-5-I-R91150 in the frontal and temporal cortices was demonstrated. Whether the decreased radioligand binding resulted from a direct competition between ketamine and I-123-5-I-R91150 or from a decreased affinity of the 5-HT2A receptor caused by ketamine remains to be elucidated.},
  author       = {Waelbers, Tim and Polis, Ingeborgh and Vermeire, Simon and Dobbeleir, André  and Eersels, Jos  and De Spiegeleer, Bart and Audenaert, Kurt and Slegers, Guido and Peremans, Kathelijne},
  issn         = {0161-5505},
  journal      = {JOURNAL OF NUCLEAR MEDICINE},
  keywords     = {ANTIDEPRESSANTS,HYPERTHYROIDISM,DOGS,LIGAND,DISORDERS,BINDING INDEX,MAJOR DEPRESSION,POSITRON-EMISSION-TOMOGRAPHY,SEROTONIN REUPTAKE INHIBITORS,CEREBRAL-BLOOD-FLOW,SPECT,5-HT2A,brain,ketamine,cats},
  language     = {eng},
  number       = {8},
  pages        = {1428--1433},
  title        = {5-HT2A Receptors in the feline brain: 123I-5-I-R91150 kinetics and the influence of ketamine measured with micro-SPECT},
  url          = {http://dx.doi.org/10.2967/jnumed.112.114637},
  volume       = {54},
  year         = {2013},
}

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