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Science to Practice |
1 Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7510. richsem{at}med.unc.edu
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The ability to measure basic tumor characteristics, such as blood flow and metabolism, holds promise for clinical radiology. To our knowledge, there are no methods available for routine quantitative measurement of tumor blood flow. In this issue of Radiology, van Laarhoven et al (1) show that measurement of the gadopentetate dimeglumine uptake rate constant kep (a measure of tumor blood flow, vascular surface area, and vascular permeability) with dynamic contrastmaterial–enhanced magnetic resonance (MR) imaging correlates inversely with the tumor metabolism measured with fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) and directly with the tumor vascular density. This article provides interesting insights into the complex relationship between blood flow and tumor metabolism.
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Dynamic contrast-enhanced MR imaging and FDG PET have been in clinical use for several years; however, there is little information in the literature on the relationship between tumor blood flow and tumor metabolism. van Laarhoven et al (1) describe an inverse correlation between these two parameters measured as the gadopentetate dimeglumine uptake rate constant kep and the FDG tumor to nontumor ratio (tumor metabolism) in colorectal liver metastases. At the same time, there was no significant correlation between tumor metabolism and tumor hypoxic fraction or in vitro measured tumor vascular density. The observed inverse correlation between tumor blood flow and tumor metabolism implies that an acute closure of tumor vessels may lead not only to a reduced supply of nutrients but also to a reduced supply of oxygen with consequent increase in tumor FDG uptake. It has been shown that tumor cells in an acutely hypoxic environment can increase their FDG uptake to survive the temporary decrease in oxygen supply (2). Closure of tumor vessels as an acute event would also explain the lack of association between FDG tumor to nontumor ratio and vascular density or hypoxic fraction. FDG uptake is determined by an acute decrease in tumor blood flow, while hypoxic fraction reflects both acute and chronic states of hypoxia. The in vitro measured vascular density is a measurement of all tumor vessels, both those that are functional and those that are not functional; thus, they do not correlate with tumor FDG tumor to nontumor ratio.
Tumor vascularization as shown on dynamic contrast-enhanced MR imaging also reflects both tumor blood flow and capillary permeability and surface area, which in itself is a physiologically interesting dynamic that has been reported previously (3).
The Practice
Clinical use.—FDG PET has been used increasingly in the diagnosis, staging, and restaging of malignant tumors; however, the sensitivity of FDG PET is about 50%–60% for tumors such as renal cell carcinoma or bronchioloalveolar lung carcinoma, although glucose is the main source of energy for these tumors. The low detectability of these tumors on FDG PET images is likely associated with their relatively slow growth pattern, their relatively high amount of noncellular components, or both, which cause a relatively low FDG count density during image acquisition (4). The data presented by van Laarhoven et al (1) describe an important association between characteristics of tumor vasculature and tumor metabolism in colorectal liver metastases, which might be extrapolated to tumors with low detectability on FDG PET images and which might provide insight into associations between metabolism and blood flow in those tumors.
Dynamic contrast-enhanced MR imaging is a useful surrogate for tumor vascularization that provides insight into the response of liver metastases to chemotherapy (5). The study by van Laarhoven et al (1) validates the use of MR imaging for this role by demonstrating correlation with vascular density.
Future opportunities and challenges.—Imaging of angiogenesis will play an important role in the assessment of tumor response to therapy because of the critical role of angiogenesis in tumor growth (6). Dynamic contrast-enhanced MR imaging has great potential for use in diagnosis of disease and monitoring of therapy. Validation of the data presented by van Laarhoven et al and new studies comparing characteristics of tumor vasculature and tumor glucose metabolism in other malignancies are required before the relationship between tumor vasculature and tumor glucose metabolism can be fully elucidated. This may reveal a complementary role for the use of dynamic contrast-enhanced MR imaging and FDG PET in the monitoring of tumor response to various treatment regimens. Quantification of vascular parameters and standardization of dynamic MR imaging protocols, as well as development of models to represent heterogeneity of blood flow within the tumor, are some of the future challenges (7).
Summary
van Laarhoven et al demonstrated an inverse relationship between the functional tumor vascularization and tumor metabolism in colorectal liver metastases (1). This will likely facilitate better understanding of tumor physiology and development of new imaging strategies in the diagnosis and treatment of cancer.
References
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