ABSTRACT
There is increasing interest in mapping receptors in vivo by using functional imaging modalities such as single photon emission tomography (SPET) and positron emission tomography (PET). Since SPET is a more accessible functional imaging modality than PET and, overall, it is more economical, radioligands suitable for this technique are in greater demand. Recently, 123I-5-I-R91150, a radioligand with high selectivity and affinity for 5-HT(2A) receptors in the brain, was introduced for SPET. This study reports on the whole-body distribution and brain uptake of the selective 123I-5-I-R91150 ligand in four normal dogs. The frontal to cerebellar ratio of uptake in time was determined in three dogs. Time-activity curve of venous blood was determined in one dog. Maximal global brain uptake was found at 10-60 min post-injection. Higher brain uptake was noted in the frontal cortical areas compared to the cerebellum. The frontal-cerebellar ratio reached the highest values at 90-180 min. Reversibility and pharmacological selectivity of ligand binding was demonstrated through displacement and blocking studies with the 5-HT(2A) receptor antagonist ketanserin. This study demonstrates that the specific 5-HT(2A) iodinated ligand can be used for imaging and semi-quantification of the 5-HT(2A) receptors in the canine brain in vivo by using SPET.
Subject(s)
Piperidines/pharmacokinetics , Radiopharmaceuticals/pharmacokinetics , Receptors, Serotonin/metabolism , Serotonin Antagonists/pharmacokinetics , Animals , Binding, Competitive/drug effects , Brain/diagnostic imaging , Dogs , Ketanserin/pharmacokinetics , Piperidines/chemical synthesis , Radiopharmaceuticals/chemical synthesis , Receptor, Serotonin, 5-HT2A , Serotonin Antagonists/chemical synthesis , Tissue Distribution , Tomography, Emission-Computed, Single-Photon , Whole-Body CountingABSTRACT
4-[123I]Iodo-N-[2-[4-(6-trifluoromethyl-2-pyridinyl)-1-piperazinyl]ethyl]benzamide (1.123I), a potential SPECT 5-HT(1A) radioligand, was evaluated in vivo in rats. Biodistribution studies were performed leading to a % ID in the brain of 0.22 at 5 min p.i. No significant differences in % ID/g tissue of the different isolated brain regions (hippocampus, hypothalamus, striatum, cortex and cerebellum) could be demonstrated. Blocking experiments with 8-OH-DPAT, WAY100635 and ketanserin could not show any significant change in tracer uptake in the isolated brain regions. These data suggest that uptake in the brain does not represent binding of 1.123I to the 5-HT(1A) receptor.
Subject(s)
Benzamides/pharmacokinetics , Brain/metabolism , Piperazines/pharmacokinetics , Receptors, Serotonin/metabolism , Serotonin Antagonists/pharmacology , Serotonin Receptor Agonists/pharmacology , Tomography, Emission-Computed, Single-Photon , 8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology , Animals , Benzamides/chemical synthesis , Brain/diagnostic imaging , Ketanserin/pharmacology , Male , Piperazines/chemical synthesis , Piperazines/pharmacology , Pyridines/pharmacology , Radioligand Assay , Rats , Rats, Sprague-Dawley , Receptors, Serotonin/drug effects , Receptors, Serotonin, 5-HT1 , Tissue DistributionABSTRACT
A high-performance liquid chromatographic procedure for the quantitation of [(123)I]Iodomethyl-N,N-diethyltamoxifen (ITX), a radioligand for human breast cancer imaging, in human plasma is described. Separation was effected on a RP-C18 column, using a mixture of acetonitrile-water-triethylamine (70/30/0.5, v/v). ITX was rapidly cleared from human plasma and metabolites appeared as early as 7.5 min p.i. Quantitative assessment of metabolites in plasma over time allowed recalculation of the ITX plasma time-activity curve. Implications of ITX metabolite formation for breast tumour imaging are discussed.
