Hyperpolarized Spectroscopic MR Shows Promise for Early Detection of Ovarian Cancer Response
Radiology authors use mouse models to advance ovarian cancer research.
Because ovarian cancer is one of the deadliest types of cancer for women, detecting response as early as possible is a critical goal of researchers.
In new Radiology research, Vikas Kundra, MD, PhD, and colleagues determined that a promising new technique - hyperpolarized carbon 13 (13C)-pyruvate MR spectroscopy — may serve as an early indicator of ovarian cancer tumor response to multi-targeted tyrosine kinase inhibitors such as pazopanib. Mouse models were used in the study; Dr. Kundra hopes to conduct similar research on humans in the future.
Pazopanib and other types of chemotherapy drugs affect tumor metabolism, an important imaging target in cancer. While physicians have traditionally looked for changes in tumor growth over time to determine treatment efficacy, earlier detection of tumor response to treatment may help provide feedback sooner and allow for quicker alteration of treatment methods when necessary.
In his research, Dr. Kundra, a professor in the Department of Radiology at the University of Texas (UT) MD Anderson Cancer Center, Houston, and colleagues initially sought to determine whether components of early and late glucose metabolism, detected via fluorine 18 (18F) fluorodeoxyglucose (FDG)-PET and hyperpolarized 13C-pyruvate MR spectroscopy, would provide indications of tumor response to pazopanib.
According to Dr. Kundra, 18F-FDG PET imaging is commonly used to study the early part of the biochemical pathway during which glucose enters the cell and is phosphorylated. Hyperpolarized 13C-pyruvate spectroscopy provides 10,000-100,000-fold or greater signal enhancement, allowing for in vivo examination of the late part of glycolysis including conversion of pyruvate to lactate.
“With this imaging method, we wanted to capture changes in tumor glucose uptake and conversion of hyperpolarized pyruvate to lactate to assess response to pazopanib,” Dr. Kundra said.
Working with approval from the UT Animal Care and Use Committee, the team performed dynamic MR spectroscopy of hyperpolarized 13C-pyruvate and 18F-FDG PET/CT on 14 female, nude mice. Human ovarian SKOV3 tumor cells were implanted into the mice. Two weeks later, they scanned all animals and began treating six of the mice with pazopanib. Seven were used for control.
Two days after start of treatment, the researchers repeated imaging and found that pazopanib inhibited tumor growth when compared with control (0.054 g +/- 0.041 vs. 0.223g +/- 0.112, respectively). In addition, a significantly higher pyruvate-to-lactate conversion was found in the treated mice than before treatment (0.46 +/- 0.07 vs. 0.31 +/- 0.14, respectively).
While results show that late stages of glucose metabolism can indicate tumor response to treatment, there was an unexpected result for the team. Early indication of response was not observed with clinically used 18F-FDG PET/CT imaging studying the early stages of glucose metabolism.
“We expected both imaging methods to detect early response but were surprised to find that only the hyperpolarized pyruvate did,” said Dr. Kundra.
Obstacles as Opportunity
One challenge researchers faced was completing the testing quickly. The window for detection of the hyperpolarized signal ranges between approximately 10 seconds and two minutes. The technique requires strict teamwork between several well-coordinated experts.
“Although timing and coordination were a challenge, they provided an opportunity to create a collaborative team of specialists such as physicists, veterinary experts, chemists and others,” he said. “Working together, they fostered new ideas and developed new and more effective working groups. The same dynamic teamwork will be necessary when this technique is brought to patients.”
Pending results of similar studies with human subjects, Dr. Kundra would like to see clinical-grade hyperpolarized 13C-pyruvate become a reality.
- Access the study, “In Vivo Assessment of Ovarian Tumor Response to Tyrosine Kinase Inhibitor Pazopanib by Using Hyperpolarized 13C-Pyruvate MR Spectroscopy and 18F-FDG PET/CT Imaging in a Mouse Model,” at http://pubs.rsna.org/doi/abs/10.1148/radiol.2017161772