[11C]PS13 PET Imaging of Neuroinflammation in Heart Failure With Reduced Ejection Fraction

Summary

Heart failure reduces the amount of blood the heart pumps, which can lead to memory and thinking problems in many patients. One possible reason is that heart failure triggers brain inflammation, a process in which certain brain immune cells (called microglia) become overactive. A heart failure medication called sacubitril-valsartan has been shown to reduce the risk of developing dementia, but it is not known whether this is because it reduces brain inflammation. This study uses a new experimental brain scan drug called \[11C\]PS13 (PS13) to measure brain inflammation directly and non-invasively, using a technique called positron emission tomography (PET). PS13 sticks to a molecule called COX-1, which is found mainly in brain immune cells (microglia). By measuring how much PS13 accumulates in the brain, researchers can estimate how much brain inflammation is present. In this pilot study, 18 patients with heart failure and mild memory or thinking problems who are being started on sacubitril-valsartan by their cardiologist (as standard clinical care) will undergo two brain PET scans: one before starting sacubitril-valsartan, and one approximately 12 weeks after. The study will also assess memory, thinking, daily function, mood, and social well-being using standard questionnaires. The study will test whether sacubitril-valsartan is associated with measurable changes in brain inflammation, and whether this type of imaging is feasible in heart failure patients. The study is funded by the American Heart Association and the National Institute on Aging, and an independent Data and Safety Monitoring Board oversees participant safety. The results will be used to design a larger study.

Timeline

Start

2026-10-01

Primary completion

2028-06-30

Completion

2028-12-31

Publications

• Background Ghazanfari N, Liow JS, Kim MJ, Cureton R, Lee A, Knoer C, Jenkins M, Hong J, Santamaria JAM, Shetty HU, Galassi A, Wighton P, Norgaard M, Greve DN, Zoghbi SS, Pike VW, Innis RB, Zanotti-Fregonara P. [11C]PS13 Demonstrates Pharmacologically Selective and Substantial Binding to Cyclooxygenase-1 in the Human Brain. J Nucl Med. 2025 Jan 3;66(1):117-122. doi: 10.2967/jnumed.124.267928.
• Background Kim MJ, Lee JH, Juarez Anaya F, Hong J, Miller W, Telu S, Singh P, Cortes MY, Henry K, Tye GL, Frankland MP, Montero Santamaria JA, Liow JS, Zoghbi SS, Fujita M, Pike VW, Innis RB. First-in-human evaluation of [11C]PS13, a novel PET radioligand, to quantify cyclooxygenase-1 in the brain. Eur J Nucl Med Mol Imaging. 2020 Dec;47(13):3143-3151. doi: 10.1007/s00259-020-04855-2. Epub 2020 May 12.
• Background Grewal PK, Abboud A, Myserlis EP, Goldschmidt ME, Butler J, Skopicki HA, Kalogeropoulos AP. Sacubitril/Valsartan and Cognitive Outcomes in Heart Failure With Reduced Ejection Fraction. JACC Adv. 2023 Jun 7;2(4):100372. doi: 10.1016/j.jacadv.2023.100372. eCollection 2023 Jun.

Drugs

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