Predosing with the unlabeled “inactive” enantiomer as a tool for improvement of the PET signal

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Abstract
In this study we investigated whether the PET signal of labeled (S)-citalopram could be improved by predosing with the unlabeled distomer (R)-citalopram. Ten minutes before intravenous injection of 1.5 MBq [(3)H]-(S)-citalopram, rats were given i.v. 0.9% saline, 16 or 24 microg (R)-citalopram. Sixty minutes after injection of [(3)H]-(S)-citalopram, the brains were dissected into eight regions. The binding obtained in each brain region was compared to cerebellum as a reference region. Predosing with saline, 16 and 24 microg (R)-citalopram yielded thalamus/cerebellum ratios of 1.6 +/- 0.12, 1.6 +/- 0.12, and 1.1 +/- 0.26 (means +/- SD), respectively. It is concluded that the nonspecific binding of radiolabeled (S)-citalopram cannot be reduced by predosing with the 150 times less active enantiomer (R)-citalopram, possibly due to the pool of nonspecific sites being too large for blocking.
Funding Information
  • 1991 Pharmacy Foundation
  • Health Insurance Fund
  • Lundbeck Foundation