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Abstract #3710

Hyperpolarized [1-13C] pyruvate as a biomarker for treatment monitoring in lymphoma murine models

Brice Tiret1,2, Adam Autry2, IlWoo Park2, Min Lu3, Rana Anjum4, Lisa Drew4, Sebastien Degorce5, Michele Mayo4, Keith Dillman4, John Kurhanewicz2, James Rubenstein3, and Myriam Chaumeil1,2

1Department of Physical Therapy and Rehabilitation Science, UCSF, San Francisco, CA, United States, 2Department of Radiology & Biomedical Imaging, UCSF, San Francisco, CA, United States, 3Helen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, CA, United States, 4Oncology Innovative Medicines and Early Development, AstraZeneca, Waltham, MA, United States, 5Oncology Innovative Medicines, AstraZeneca, Cheshire, United Kingdom

In primary CNS lymphoma (PCNSL), MYD88 mutation is the most common, and induces a constitutive activation of IRAK4 and NF-kB signaling. AZ1495, a IRAK4 inhibitor, significantly improved OS in MYD88mut PCNSL models, highlighting the clinical potential of IRAK inhibition. However, monitoring of such targeted therapies remains challenging using conventional imaging. Because NF-kB controls metabolism, we questioned if hyperpolarized 13C MRSI could monitor IRAK inhibition in PCNSL. We show that HP-13C MRSI was able to detect a decreased HP lactate production following IRAK inhibition in MYD88mut tumors, not wild-types, highlighting the potential of metabolic imaging for monitoring therapy response in lymphomas.

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