In vivo biodistribution of a radiotracer for imaging serotonin-1a receptor sites with pet: [11C]Ly274601
1998; Elsevier BV; Volume: 63; Issue: 17 Linguagem: Inglês
10.1016/s0024-3205(98)00420-2
ISSN1879-0631
AutoresMakiko Suehiro, Mark D. Underwood, Victoria Arango, Theodore S. Wang, Suham Kassir, Mihran J. Bakalian, Tami Yatabe, Mali Pratap, Ronald L. Van Heertum, J. John Mann,
Tópico(s)Neuroscience and Neuropharmacology Research
ResumoLY274601 [R-(+)8-thiomethyl-2-(di-n-propyl-amino)tetralin], a full agonist of the 5-HT1A receptor with high affinity and selectivity, was labeled with 11C and 3H, and its in vivo behavior was studied to evaluate [11C]LY274601 as a PET radiotracer for imaging 5-HT1A receptor sites in living brain. Following intravenous tail injection into mice, [11C]LY274601 showed high blood-brain barrier permeability and accumulated in regions known to have high densities of 5-HT1A receptor sites such as the brain stem including the raphe nuclei. The binding of the radiotracer in target tissues is blocked by pre-injection of the 5-HT1A receptor selective ligand 8-OH-DPAT (1 mgkg, sc), suggesting that the binding is specific to 5-HT1A receptor sites. Using ex vivo autoradiography, the target tissues such as hippocamous CA1-4 fields, piriform cortex, dorsal raphe nucleus and lateral septum were visualized as hot spots. These tissues were observed to have binding 2–2.7 times greater than the cerebellum. The distribution of the radiotracer agrees well with the distribution of 5-HT1A receptors revealed by in vitro autoradiography with [3H]8-OH-DPAT. However, the radiotracer was metabolized quickly and cleared from target tissues with a half life of approximately 15 min. [11C]LY274601 showed high non-specific binding in regions with low number of 5-HT1A receptor sites such as cerebellum.
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