Noninvasive Assessment of Renal Tumor Aggressiveness Using Hyperpolarized 13C MR
Abstract
The incidence of renal cell carcinomas (RCCs) has risen significantly in the last 20 years. There is currently a critical unmet need for noninvasive biomarkers that can confidently predict the biological behavior of renal tumors in order to improve their accurate diagnosis and rational selection of treatment options. The goal of this pre-clinical study is to identify clinically translatable hyperpolarized 13C markers of RCC aggressiveness using established cell lines. In this work, we compared the metabolism of living immortalized cells derived from a localized renal cell carcinoma (RCC), and a metastatic RCC using hyperpolarized 13C pyruvate MR in a MR compatible bioreactor. We showed that the observed hyperpolarized pyruvate to lactate flux in these cells is likely influenced by a combination of factors including the enzyme lactate dehydrogenase (LDH), and the monocarboxylate transporters (MCT) 1 and 4 which transport pyruvate and lactate respectively. We further demonstrated that cells derived from the metastatic RCC have increased export of hyperpolarized lactate to the extracellular space compared to the cells derived from the localized RCC, and that such differences are likely mediated by the differential expression of MCT4. These results suggest that the assessment of lactate production and export using clinically translatable hyperpolarized probes has the potential to improve the noninvasive characterization of renal tumor aggressiveness.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2012
- Accession Number
- ADA566862
Entities
People
- Zhen Wang
Organizations
- University of California, San Francisco