Research presented Wednesday suggests that hyperpolarized [1-13C]pyruvate MRI can be used to detect pancreatic cancer in its premalignant and early stages by measuring the dynamic altered metabolism of pyruvate to lactate.
Murley
"We chose to study this topic because of the large mortality and late presentation of pancreatic cancer," said Grace Murley (formerly Grace Isakson), BA, BS, a graduate research assistant at UTHealth Houston Graduate School of Biomedical Sciences/MD Anderson Cancer Center in Houston.
"There is only an 11% 5-year survival rate of patients diagnosed with pancreatic cancer," she continued. "This is in part due to the aggressiveness of the cancer and its asymptomatic nature until late-stage disease. My advisor, Pratip Bhattacharya, PhD, has been working on hyperpolarized MRI for use in metabolic imaging for many years, and came up with the idea of looking for a metabolic shift in pre-malignant pancreatic lesions."
Rather than only monitoring tumor growth, the researchers combined anatomical and metabolic MR imaging with the goal of detecting pancreatic cancer early. They genetically engineered three mouse models to develop pre-invasive pancreatic intraepithelial neoplasia (PanIn) precursor lesions (KC), invasive pancreatic cancer (KPC) and no lesion (control), respectively. They also engineered a fourth model to develop intraepithelial papillary mucinous neoplasia (IPMN) lesions as a result of doxycycline induction.
The investigators performed dynamic nuclear polarization on hyperpolarized [1-13C]pyruvate MRI for hyperpolarization to enhance the signal. They then acquired the expected pyruvate 13C MR spectra over the area of interest with a 7T Bruker MRI scanner.
Murley and colleagues acquired images for the PanIN models when the mice were ages 14, 21 and 28 weeks. In addition, they took images at seven weeks for the IPMN mouse models that received doxycycline (Dox+) and those that did not receive doxycycline (Dox-).
Results Point to Opportunities for Improved Patient Care
In KC models, the lactate-to-pyruvate ratio increased in comparison to the control model during progression from low-grade PanIN to high-grade PanIN. The researchers also found a significant increase in the lactate-to-pyruvate ratio (0.35) for the first time point (0.27) in the KPC mouse model.
A representative image from a PanIN mouse model with corresponding hyperpolarized pyruvate spectra. A) Anatomical images obtained on MRI via T2_RARE sequence, 17 slices, 10 mm/slice with coronal slicing of a PanIN mouse. The blue square indicates the area used for metabolic imaging and was selected to incorporate the pancreas. Image courtesy of Grace Murley, BA, BS
In addition, there was a significant increase in the second time point lactate-to-pyruvate ratio for the KPC model compared to KC (0.26) as well as control mice (0.15). Finally, there was a statistically significant difference in the lactate to pyruvate ratio between Dox+ mice and Dox-mice (p=0.007) as demonstrated by the IPMN model.
Based on these findings, Murley concluded that the transformation from normal pancreatic tissue to premalignant pancreatic lesions can be detected by observing the metabolic shift toward lactic acid production.
"We were able to see the shift before the presence of visible lesions in the pancreatic intraepithelial neoplasia model," she said. "This is very promising, given that diagnosing pancreatic cancer before the presence of symptoms is so challenging."
The results indicate that it may be possible to detect neoplasia even before the development of malignancy, which could lead to noninvasive early detection of pancreatic premalignant lesions in patients, Murley said.
"We are excited to start clinical trials with a high-risk pancreatic cancer clinic at MD Anderson," she added.
Murley acknowledged the contributions of her fellow researchers, including Jose Enriquez, MD; Prasanta Dutta, PhD; Florencia McAllister, MD; and Pratip Bhattacharya, MD.
Access the presentation, "Real-Time Metabolic Imaging Biomarkers for Detection of Pancreatic Premalignant Lesions," (WSA-STCE-3) on demand at Meeting.RSNA.org.
