1) Rapid Chemical Shift Imaging: Hyperpolarized MRI of 13C-labeled tracers is an emerging technique to non-invasively visualize metabolism of exogenously injected substrates such as 13C labeled pyruvate. Since the MRI signal from the hyperpolarized pyruvate lasts for time intervals less than 2 minutes, earlier work was conducted based on assumptions of the pharamacokinetics of the injected tracer in the animal or injecting the tracer to obtain such information followed by a second injection for metabolic imaging. To overcome this problem and conduct both pharamacokinetic assessment as well as metabolic imaging, we developed and implemented rapid chemical shift imaging capabilities. Based on an Echo planar imaging sequence for hyperpolarized 13C-MRI The NMR signal of hyperpolarized 13C-labeled agents lasts only 2-3 min after injection, and currently available gradient echo based chemical shift imaging (CSI), which takes 15-20 sec for data acquisition, is not fast enough to trace the dynamics of the metabolism. We have developed and optimized the MRI pulse sequence of echo planar based spectroscopic imaging (EPSI), which can now obtain 2D metabolic images every 2-5 sec. 2. Detection of early treatment response to anti-angiogenic therapy. Typical criteria for cancer treatment response can not to applied to anti-angiogenic therapy which is cytostatic than cytotoxic. We have investigated if hyperpolarized 13C MRI of pyruvate can detect the response of SCCVII tumor to anti-angiogenic drug sunitinib. Flux of pyruvate-to-lactate conversion significantly slowdown 2 and 4 days after sunitinib treatment, and western blot analysis suggested the underlying mechanism of decreased pyruvate dehydrogenase kinase-1 (PDK-1) expression and resultant up-regulation of mitochondrial pyruvate usage. 3. Detection of tumor response to radiation therapy We also applied the pyruvate metabolic imaging to detect treatment response to radiation. Tumor pyruvate-lactate conversion rate transiently increased 24 hr after 10Gy x-irradiation, then decreased continuous 3 fractions of 10Gy/day (total 30Gy) irradiation. We are investigating underlying mechanism of this pyruvate metabolic change after radiation therapy.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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National Cancer Institute Division of Basic Sciences
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Read, Graham H; Miura, Natsuko; Carter, Jenna L et al. (2018) Three-dimensional alginate hydrogels for radiobiological and metabolic studies of cancer cells. Colloids Surf B Biointerfaces 171:197-204
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