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.