Multifunctional imaging signature for V-KI-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in colorectal cancer.

UNLABELLED: This study explores the potential for multifunctional imaging to provide a signature for V-KI-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutations in colorectal cancer. METHODS: This prospective study approved by the institutional review board comprised 33 patients undergoing PET/CT before surgery for proven primary colorectal cancer. Tumor tissue was examined histologically for presence of the KRAS mutations and for expression of hypoxia-inducible factor-1 (HIF-1) and minichromosome maintenance protein 2 (mcm2). The following imaging parameters were derived for each tumor: (18)F-FDG uptake ((18)F-FDG maximum standardized uptake value [SUVmax]), CT texture (expressed as mean of positive pixels [MPP]), and blood flow measured by dynamic contrast-enhanced CT. A recursive decision tree was developed in which the imaging investigations were applied sequentially to identify tumors with KRAS mutations. Monte Carlo analysis provided mean values and 95% confidence intervals for sensitivity, specificity, and accuracy. RESULTS: The final decision tree comprised 4 decision nodes and 5 terminal nodes, 2 of which identified KRAS mutants. The true-positive rate, false-positive rate, and accuracy (95% confidence intervals) of the decision tree were 82.4% (63.9%-93.9%), 0% (0%-10.4%), and 90.1% (79.2%-96.0%), respectively. KRAS mutants with high (18)F-FDG SUVmax and low MPP showed greater frequency of HIF-1 expression (P = 0.032). KRAS mutants with low (18)F-FDG SUV(max), high MPP, and high blood flow expressed mcm2 (P = 0.036). CONCLUSION: Multifunctional imaging with PET/CT and recursive decision-tree analysis to combine measurements of tumor (18)F-FDG uptake, CT texture, and perfusion has the potential to identify imaging signatures for colorectal cancers with KRAS mutations exhibiting hypoxic or proliferative phenotypes.

Imaging assessment of lung tumor angiogenesis: insights and innovations.

Lung cancer is the leading cause of cancer death in the United States. It is estimated that more than 228,000 new cases will be diagnosed in 2013, accounting for approximately 159,000 or 27% of all cancer deaths. Survival in these patients remains poor despite advances in surgery, definitive radiotherapy, and chemotherapy for primary and metastatic non-small cell lung cancer. Five-year relative survival rates remain at 27% for regional disease and 54% for node-negative disease. With the increasing personalization of therapy, there remains a need for better prognostic and predictive markers to direct patient management in lung cancer. Hypoxia and angiogenesis play an important role in the development and progression of lung cancer. Targeted and non-targeted imaging techniques in the preclinical and clinical setting, combined with advanced postprocessing techniques to assess tumor heterogeneity, may enable clinicians to better characterize lung tumors, and to predict and assess response to treatment. In this review, we summarize our current understanding of angiogenesis in lung cancer and discuss the available imaging techniques to assess this in the preclinical and clinical setting.

CT perfusion in oncologic imaging: a useful tool?

OBJECTIVE: This article summarizes the current status of CT perfusion in oncologic imaging, including lesion characterization, staging, prediction of patient outcome or response to therapy, assessment of response to different therapies, and evaluation of tumor relapse. Technical limitations and drawbacks of CT perfusion are also discussed. CONCLUSION: Tumor angiogenesis is essential for cancer growth and provides an attractive target for oncologic therapies. CT perfusion is an emerging imaging tool that provides both qualitative and quantitative information regarding tumor angiogenesis.

Novel oncologic drugs: what they do and how they affect images.

Targeted therapies are designed to interfere with specific aberrant biologic pathways involved in tumor development. The main classes of novel oncologic drugs include antiangiogenic drugs, antivascular agents, drugs interfering with EGFR-HER2 or KIT receptors, inhibitors of the PI3K/Akt/mTOR pathway, and hormonal therapies. Cancer cells usurp normal signal transduction pathways used by growth factors to stimulate proliferation and sustain viability. The interaction of growth factors with their receptors activates different intracellular pathways affecting key tumor biologic processes such as neoangiogenesis, tumor metabolism, and tumor proliferation. The response of tumors to anticancer therapy can be evaluated with anatomic response assessment, qualitative response assessment, and response assessment with functional and molecular imaging. Angiogenesis can be measured by means of perfusion imaging with computed tomography and magnetic resonance (MR) imaging. Diffusion-weighted MR imaging allows imaging evaluation of tumor cellularity. The main imaging techniques for studying tumor metabolism in vivo are positron emission tomography and MR spectroscopy. Familiarity with imaging findings secondary to tumor response to targeted therapies may help the radiologist better assist the clinician in accurate evaluation of tumor response to these anticancer treatments. Functional and molecular imaging techniques may provide valuable data and augment conventional assessment of tumor response to targeted therapies. Supplemental material available at http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.317115108/-/DC1.

Investigating vulnerable atheroma using combined (18)F-FDG PET/CT angiography of carotid plaque with immunohistochemical validation.

UNLABELLED: Inflammation and angiogenesis are hypothesized to be important factors contributing to plaque vulnerability, whereas calcification is suggested to confer stability. To investigate this in vivo, we combined CT angiography and PET and compared the findings with immunohistochemistry for patients undergoing carotid endarterectomy. METHODS: Twenty-one consecutive patients (18 men, 3 women; mean age ± SD, 68.3 ± 7.3) undergoing carotid endarterectomy were recruited for combined carotid (18)F-FDG PET/CT angiography. Plaque (18)F-FDG uptake was quantified with maximum standardized uptake value, and CT angiography quantified percentage plaque composition (calcium and lipid). Surgical specimens underwent ex vivo CT aiding image registration, followed by immunohistochemical staining for CD68 (macrophage density) and vascular endothelial growth factor (angiogenesis). Relationships between imaging and immunohistochemistry were assessed with Spearman rank correlation and multivariable regression. RESULTS: The mean (±SD) surgically excised carotid plaque (18)F-FDG metabolism was 2.4 (±0.5) versus 2.2 (±0.3) contralaterally (P = 0.027). There were positive correlations between plaque (18)F-FDG metabolism and immunohistochemistry with CD68 (ρ = 0.55; P = 0.011) and vascular endothelial growth factor (ρ = 0.47; P = 0.031). There was an inverse relationship between plaque (18)F-FDG metabolism and plaque percentage calcium composition on CT (ρ = -0.51; P = 0.018) and between calcium composition and immunohistochemistry with CD68 (ρ = -0.57; P = 0.007). Regression showed that maximum standardized uptake value and calcium composition were independently significant predictors of angiogenesis, and calcium composition was a predictor of macrophage density. CONCLUSION: We provide in vivo evidence that increased plaque metabolism is associated with increased biomarkers of angiogenesis and inflammation, whereas plaque calcification is inversely related to PET and histologic biomarkers of inflammation.