[11C]ATR-101 PET imaging to identify macrophage differentiation to foam cell

Conclusion: ACAT1 inhibitors [11C]ATR-101 and [18F]ATR-F were synthesized. Biodistribution studies showed good adrenal uptake for both agents. [11C]ATR-101 when administered to (healthy) C57BL6 and (atherosclerotic) ApoE-/- mice could easily distinguish the diseased animal from the healthy control. Future studies will use PET/CT for additional structural information, and [18F]ATR-F will be used in longer imaging studies. References: (1) Yu, X.-H.; Fu, Y.-C.; Zhang, D.-W.; Yin, K.; Tang, C.-K. Foam Cells in Atherosclerosis. Clin. Chim. Acta 2013, 424, 245-252.(2) Trivedi, B. K.; Purchase, T. S.; Holmes, A.; Augelli-szafran, C. E.; Essenburg, A. D.; Hamelehle, K. L.; Stanfield, R. L.; Bousley, R. F.; Krauset, B. R. Inhibitors of Acyl-CoA:Cholesterol Acyltransferase (ACAT). 7. Development of a Series of’ Substituted N-Phenyl-"-[ (l-Phenylcyclopentyl)Methyl]Ureas with Enhanced Hypocholesterolemic Activity1. 1994, 51 (Scheme 2), 1652-1659.(3) Nevanimibe selectively targets adrenal steroidogenesis to treat serious orphan diseases https://millendo.com/pipeline/nevanimibe/ (accessed Nov 15, 2019).(4) Makaravage, K. J.; Brooks, A. F.; Mossine, A. V; Sanford, M. S.; Scott, P. J. H. Copper-Mediated Radiofluorination of Arylstannanes with [18F]KF. Org. Lett. 2016, 18 (20), 5440-5443. Acknowledgements: We thank Jenelle Stauff, Janna Arteaga, and Phillip Sherman for conducting animal imaging studies
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Preclinical Probes for Cardiovascular, Endocrine & amp; Other Source Type: research