Imaging the Enzyme 11β-Hydroxysteroid Dehydrogenase Type 1 with PET: Evaluation of the Novel Radiotracer 11C-AS2471907 in Human Brain
| Autor: | Teresa Lara-Jaime, Beata Planeta, David Matuskey, Richard E. Carson, Jim Ropchan, Anupama Shirali, Shannan Henry, Yiyun Huang, Susan Bellaire, Michael Kapinos, David Labaree, Jean-Dominique Gallezot, Mark Walzer, Richard Pracitto, Nabeel Nabulsi, Gerard J. Marek, Hong Gao, Shu-fei Lin, Nancy Yuan |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty biology Chemistry Putamen Thalamus Caudate nucleus Human brain White matter 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Endocrinology 11β-hydroxysteroid dehydrogenase type 1 Cortex (anatomy) Internal medicine medicine biology.protein Cingulum (brain) Radiology Nuclear Medicine and imaging 030217 neurology & neurosurgery |
| Zdroj: | Journal of Nuclear Medicine. 60:1140-1146 |
| ISSN: | 2159-662X 0161-5505 |
| Popis: | The 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme converts cortisone to cortisol and participates in the regulation of glucocorticoid levels in tissues. 11β-HSD1 is expressed in the liver, kidney, adipose tissue, placenta, and brain. 11β-HSD1 is a target for treatment of depression, anxiety, posttraumatic stress disorder, and also against age-related cognitive function and memory loss. In this study, we evaluated the radiotracer 11C-AS2471907 (3-(2-chlorophenyl)-4-(methyl-11 C)-5-[2-[2,4,6-trifluorophenoxy]propan-2-yl]-4H-1,2,4-triazole) to image 11β-HSD1 availability in the human brain with PET. Methods: Fifteen subjects were included in the study. All subjects underwent one 2-h scan after a bolus administration of 11C-AS2471907. Two subjects underwent an additional scan after blockade with the selective and high-affinity 11β-HSD1 inhibitor ASP3662 to evaluate 11C-AS2471907 nondisplaceable distribution volume. Five subjects also underwent an additional scan to evaluate the within-day test-retest variability of 11C-AS2471907 volumes of distribution (V T). Results: 11C-AS2471907 time-activity curves were best fitted by the 2-tissue-compartment (2TC) model. 11C-AS2471907 exhibited a regionally varying pattern of uptake throughout the brain. The V T of 11C-AS2471907 ranged from 3.7 ± 1.5 mL/cm3 in the caudate nucleus to 14.5 ± 5.3 mL/cm3 in the occipital cortex, with intermediate values in the amygdala, white matter, cingulum, insula, frontal cortex, putamen, temporal and parietal cortices, cerebellum, and thalamus (from lowest to highest V T). From the blocking scans, nondisplaceable distribution volume was determined to be 0.16 ± 0.04 mL/cm3 for 11C-AS2471907. Thus, nearly all uptake was specific and the binding potential ranged from 22 in the caudate to 90 in the occipital cortex. Test-retest variability of 2TC V T values was less than 10% in most large cortical regions (14% in parietal cortex) and ranged from 14% (cerebellum) to 51% (amygdala) in other regions. The intraclass correlation coefficient of 2TC V T values ranged from 0.55 in the white matter to 0.98 in the cerebellum. Conclusion: 11C-AS2471907 has a high fraction of specific binding in vivo in humans and reasonable within-day reproducibility of binding parameters. |
| Databáze: | OpenAIRE |
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