New Imaging Technique Measures Breast Cancer Metabolism

New Imaging Technique Measures Breast Cancer Metabolism

A new imaging technique that uses magnetized particles to see in real time which regions of a tumor are active is feasible in breast cancer, a small study shows.

The technology, if used along with existing clinical tools, could allow for more individualized treatments and earlier detection of responses to treatment.

The study, “Imaging breast cancer using hyperpolarized carbon-13 MRI,” was published in Proceedings of the National Academy of Sciences (PNAS).

Cancer cells are defined by their constant state of growth, and growing at such a high rate requires a lot of energy. That means tumor cells have a metabolic profile distinct from other types of cells in the body; this metabolic shift is called the Warburg effect. Tumor cells get much of their energy through lactate fermentation, which involves the conversion of the molecule pyruvate into lactate.

Because metabolism affects tumor growth so profoundly, understanding the metabolic profile of a given tumor could provide valuable prognostic information. However, actually measuring a tumor’s metabolism in a clinical setting hasn’t been technologically feasible until recently.

The researchers used a technique called carbon-13 magnetic resonance spectroscopic imaging (MRSI) to assess the metabolism of breast tumors.

They used carbon-13 pyruvate, a form of pyruvate that is slightly heavier than the most common form that occurs in nature. By cooling it to extremely low temperatures and exposing it to a strong magnetic field, the carbon-13 pyruvate becomes hyperpolarized — essentially, magnetized.

The hyperpolarized carbon-13 pyruvate is put in a solution and injected into the bloodstream. Then it can be tracked using an MRI scan.

The technique has been demonstrated to be feasible in brain and prostate cancers, but has never been tested in people with breast cancer.

The researchers used a form of MRI called magnetic resonance spectroscopic imaging (MRSI) to evaluate the tumors of seven people with various types and grades of breast cancer.

They focused on three metabolic metrics: the signal-to-noise ratios (SNRs) of pyruvate and lactate individually, and the ratio of lactate to pyruvate (LAC/PYR). SNR compares the level of a desired signal to the level of background noise. A higher ratio generally provides better MRSI images.

In all participants, a lactate signal was only detected within the tumors. This was expected, given the unique metabolic traits of tumor cells.

There was a fair amount of variation in all three metrics among the seven tumors assessed. The SNR of pyruvate ranged from 6.2 to 74.3, the SNR of lactate ranged from -0.1 to 22.3, and the LAC/PYR ratio ranged from 0.021 to 0.473.

In one of the larger tumors, variations were observed within the tumor itself. Such intratumoral heterogeneity is an established feature of many tumors at nearly all levels.

The LAC/PYR ratios correlated significantly with tumor size, as well as with two metabolism-associated proteins, MCT1 and HIF1a. The SNR of lactate also correlated significantly with tumor size.

“This study, although in a relatively small cohort, demonstrates the feasibility and safety of [MRSI] in patients with early breast cancer,” the researchers said.

“This is one of the most detailed pictures of the metabolism of a patient’s breast cancer that we’ve ever been able to achieve. It’s like we can see the tumor ‘breathing,'” study co-author Kevin Brindle, a professor at the Cancer Research UK Cambridge Institute, said in a press release.

Combining this kind of scan with ongoing advances in genetic testing could allow for treatment that is more tailored to the individual, Brindle said. Monitoring tumor metabolism could also allow clinicians to determine whether a person is responding to a treatment more quickly than is currently possible, he said.

“This exciting advance in scanning technology could provide new information about the metabolic status of each patient’s tumor upon diagnosis, which could help doctors to identify the best course of treatment,” said Charles Swanton, PhD, chief clinician at Cancer Research UK.

“Ultimately, the hope is that scans like this could help doctors decide to switch to a more intensive treatment if needed, or even reduce the treatment dose, sparing people unnecessary side effects,” said Swanton, who was not directly involved in the study.