Abstract #2438

Early detection of photoimmunotherapy-induced tumor cell death with hyperpolarized [1,4-13C2]fumarate

Shun Kishimoto¹, Jeeva Munasinghe², Marcelino Bernardo¹, Hellmut Merkle³, Keita Saito¹, James B Mitchell¹, Jan Henrik Ardenkjaer-Larsen⁴, Peter L Choyke¹, and Murali Cherukuri¹

¹NCI, Bethesda, MD, United States, ²NINDS, Bethesda, MD, United States, ³LFMI, Bethesda, MD, United States, ⁴GE Health Care, brondby, Denmark

Photoimmunotherapy (PIT) is a novel therapy for cancer treatment. PIT combines a targeted antibody with the photon absorber, IR700, which, after exposure to near infrared (NIR) light induces highly selective tumor necrosis with almost no side effects to normal adjacent tissue. PIT is now in Phase I clinical trials in head and neck cancers. Although NIR PIT can be highly effective, the size of the lesion does not immediately change and it may take several weeks for the tumor to completely respond anatomically. Thus, detecting early therapeutic response in the absence of anatomic change is of interest. Here, we demonstrate the effects of NIR PIT on 13C magnetic resonance spectroscopy (MRS) in an animal model (EGFR positive A431 tumor) using 13C labeled hyperpolarized (HP) pyruvate and fumarate. Interestingly, the lactate-to-pyruvate ratio was almost unchanged, while the malate-to-fumarate ratio showed a significant difference in PIT treated tumors. This is explained by the difference of the bio distribution of these tracers. Hyperpolarized 13C labeled fumarate MRS is a promising method for detecting early PIT mediated cell necrosis.

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