BJC: Hyperpolarized 13C-labeled substrates detect breast cancer treatment response

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A combination of hyperpolarized [1-13C]pyruvate and [1,4-13C2]fumarate can be used to detect response to doxorubicin treatment before there is any detectable change in tumor size in a model of human breast adenocarcinoma, according to results published in the Oct. 26 issue of British Journal of Cancer.

Dynamic nuclear polarization (DNP) has permitted noninvasive imaging of tumor cell metabolism in vivo, following injection of a hyperpolarized 13C-labelled cell substrate, and there is increased sensitivity of magnetic resonance spectroscopy to image the molecule in vivo, and, more importantly, its metabolic conversion into other cell metabolites, according to researchers.

Changes in hyperpolarised [1-13C]pyruvate and [1,4-13C2]fumarate metabolism were evaluated in both MDA-MB-231 cells and in mice implanted with MDA-MB-231 tumors following doxorubicin treatment by Kevin Brindle, PhD, professor in the department of biochemistry, University of Cambridge in England, and senior group leader in the Cancer Research U.K. Cambridge Research Institute, and colleagues.

Brindle and colleagues used two 13C-labelled markers - [1-13C]pyruvate and [1,4-13C2]fumarate that were involved in cellular processes and are targeted by doxorubicin, highlighting the early effects that the drug is having on cancer cells.

The first marker, [1-13C]pyruvate showed that doxorubicin incuded apoptosis, which was accompanied by a decrease in hyperpolarised 13C label flux between [1-13C]pyruvate and lactate.

The second marker, [1,4-13C2]fumarate, showed that doxorubicin was killing cancer cells, as it is only converted into another molecule called malate in cells that are dying due to cancer treatment.

In vivo, the decrease in 13C label exchange between pyruvate and lactate and the increased flux between fumarate and malate, following drug treatment, were shown to occur in the absence of any detectable change in tumor size.

“There has been a need to develop imaging methods that can detect treatment response more accurately and before tumors change size. Our new imaging method not only shows early evidence that treatment is working but could also help predict the long term outcome. We expect that these techniques will have an impact for patients in the near future,” said Brindle.

“We need fast and accurate ways of knowing that the treatment is working. This research could help us tailor treatment to each patient by giving doctors a useful tool to check treatments are working after a short time, rather than waiting several weeks to see if the tumour is shrinking, reducing unnecessary treatment for women,” said Lesley Walker, PhD, director of cancer information at Cancer Research U.K.

This imaging technique was developed in conjunction with GE Healthcare.