Abstract #3710

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

Brice Tiret^1,2, Adam Autry², IlWoo Park², Min Lu³, Rana Anjum⁴, Lisa Drew⁴, Sebastien Degorce⁵, Michele Mayo⁴, Keith Dillman⁴, John Kurhanewicz², James Rubenstein³, and Myriam Chaumeil^1,2

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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