Noncompartmental and compartmental modeling of the kinetics of carbon-11 labeled pyrilamine in the human brain

Zsolt Szabo, H. T. Ravert, I. Gozukara, W. Geckle, C. Seki, S. Sostre, P. Peller, L. Monsein, T. K. Natarajan, Jonathan M Links, Dean Foster Wong, Robert F Dannals, H. N. Wagner

Research output: Contribution to journalArticle

Abstract

The kinetic pattern of a 11C-labeled histamine H1 receptor antagonist, [11C]pyrilamine, was investigated in the human brain by factor analysis of dynamic PET studies. Tissue time activity curves were also processed by compartment model curve fitting preceded by deconvolution analysis. Factor analysis revealed two statistically significant and physiologically meaningful kinetic patterns: one for specific and another for nonspecific binding of the radioligand. From these two factors a compartment model containing two tissue compartments (one for specific binding and another for nonspecific binding and free ligand) was constructed. The two-compartment model was also supported by the impulse response function, which was obtained by deconvolution and showed two components. The factor image constructed from factor two demonstrated a distribution pattern characteristic for brain regions rich (frontal, parietal, and temporal lobes) or poor (occipital lobe and cerebellum) in H1 receptors. Blockade of H1 receptors with unlabeled pyrilamine, diphenhydramine, or hydroxyzine caused a significant reduction of this factor. Blockade produced no significant changes in factor one representing nonspecific binding. We conclude that the kinetics of [11C]pyrilamine in the brain can be described by two tissue compartments, one related to the distribution of the H1 receptors. Factor analysis of dynamic studies can be used to locally separate these two compartments, for identification of regions rich and poor in H1 receptors and for noninvasive quantitative investigation of the effects of H1 receptor blockers such as pyrilamine, diphenhydramine, or hydroxyzine.

Original languageEnglish (US)
Pages (from-to)263-275
Number of pages13
JournalSynapse
Volume15
Issue number4
DOIs
StatePublished - 1993

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Pyrilamine
Histamine H1 Receptors
Carbon
Hydroxyzine
Brain
Statistical Factor Analysis
Diphenhydramine
Histamine H1 Antagonists
Occipital Lobe
Parietal Lobe
Frontal Lobe
Temporal Lobe
Cerebellum
Ligands

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pharmacology

Cite this

Szabo, Z., Ravert, H. T., Gozukara, I., Geckle, W., Seki, C., Sostre, S., ... Wagner, H. N. (1993). Noncompartmental and compartmental modeling of the kinetics of carbon-11 labeled pyrilamine in the human brain. Synapse, 15(4), 263-275. https://doi.org/10.1002/syn.890150403

Noncompartmental and compartmental modeling of the kinetics of carbon-11 labeled pyrilamine in the human brain. / Szabo, Zsolt; Ravert, H. T.; Gozukara, I.; Geckle, W.; Seki, C.; Sostre, S.; Peller, P.; Monsein, L.; Natarajan, T. K.; Links, Jonathan M; Wong, Dean Foster; Dannals, Robert F; Wagner, H. N.

In: Synapse, Vol. 15, No. 4, 1993, p. 263-275.

Research output: Contribution to journalArticle

Szabo, Z, Ravert, HT, Gozukara, I, Geckle, W, Seki, C, Sostre, S, Peller, P, Monsein, L, Natarajan, TK, Links, JM, Wong, DF, Dannals, RF & Wagner, HN 1993, 'Noncompartmental and compartmental modeling of the kinetics of carbon-11 labeled pyrilamine in the human brain', Synapse, vol. 15, no. 4, pp. 263-275. https://doi.org/10.1002/syn.890150403
Szabo, Zsolt ; Ravert, H. T. ; Gozukara, I. ; Geckle, W. ; Seki, C. ; Sostre, S. ; Peller, P. ; Monsein, L. ; Natarajan, T. K. ; Links, Jonathan M ; Wong, Dean Foster ; Dannals, Robert F ; Wagner, H. N. / Noncompartmental and compartmental modeling of the kinetics of carbon-11 labeled pyrilamine in the human brain. In: Synapse. 1993 ; Vol. 15, No. 4. pp. 263-275.
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AU - Seki, C.

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