Correlation of PET images of metabolism, proliferation and hypoxia to characterize tumor phenotype in patients with cancer of the oropharynx

University of Wisconsin, Madison, USA. Electronic address: .
Radiotherapy and Oncology (Impact Factor: 4.86). 10/2012; 105(1). DOI: 10.1016/j.radonc.2012.09.012
Source: PubMed

ABSTRACT Spatial organization of tumor phenotype is of great interest to radiotherapy target definition and outcome prediction. We characterized tumor phenotype in patients with cancers of the oropharynx through voxel-based correlation of PET images of metabolism, proliferation, and hypoxia. METHODS: Patients with oropharyngeal cancer received (18)F-fluorodeoxyglucose (FDG) PET/CT, (18)F-fluorothymidine (FLT) PET/CT, and (61)Cu-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) PET/CT. Images were co-registered and standardized uptake values (SUV) were calculated for all modalities. Voxel-based correlation was evaluated with Pearson's correlation coefficient in tumor regions. Additionally, sensitivity studies were performed to quantify the effects of image segmentation, registration, noise, and segmentation on R. RESULTS: On average, FDG PET and FLT PET images were most highly correlated (R(FDG:FLT)=0.76, range 0.53-0.85), while Cu-ATSM PET showed greater heterogeneity in correlation to other tracers (R(FDG:Cu-ATSM)=0.64, range 0.51-0.79; R(FLT:Cu-ATSM)=0.61, range 0.21-0.80). Of the tested parameters, correlation was most sensitive to image registration. Misregistration of one voxel lead to ΔR(FDG)=0.25, ΔR(FLT)=0.39, and ΔR(Cu-ATSM)=0.27. Image noise and reconstruction also had quantitative effects on correlation. No significant quantitative differences were found between GTV, expanded GTV, or CTV regions. CONCLUSIONS: Voxel-based correlation represents a first step into understanding spatial organization of tumor phenotype. These results have implications for radiotherapy target definition and provide a framework to test outcome prediction based on pretherapy distribution of phenotype.

1 Follower
  • [Show abstract] [Hide abstract]
    ABSTRACT: In lung cancer, tumor hypoxia is a characteristic feature, which is associated with a poor prognosis and resistance to both radiation therapy and chemotherapy. As the development of tumor hypoxia is associated with decreased perfusion, perfusion measurements provide more insight into the relation between hypoxia and perfusion in malignant tumors. Positron emission tomography (PET) is a highly sensitive nuclear imaging technique that is suited for non-invasive in vivo monitoring of dynamic processes including hypoxia and its associated parameter perfusion. The PET technique enables quantitative assessment of hypoxia and perfusion in tumors. To this end, consecutive PET scans can be performed in one scan session. Using different hypoxia tracers, PET imaging may provide insight into the prognostic significance of hypoxia and perfusion in lung cancer. In addition, PET studies may play an important role in various stages of personalized medicine, as these may help to select patients for specific treatments including radiation therapy, hypoxia modifying therapies, and antiangiogenic strategies. In addition, specific PET tracers can be applied for monitoring therapy. The present review provides an overview of the clinical applications of PET to measure hypoxia and perfusion in lung cancer. Available PET tracers and their characteristics as well as the applications of combined hypoxia and perfusion PET imaging are discussed.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The subtle hypoxia underlying chronic cardiovascular disease is an attractive target for PET imaging, but the lead hypoxia imaging agents 64CuATSM and 18FMISO trapped only at extreme levels of hypoxia and hence are insufficiently sensitive for this purpose. We have therefore sought an analog of 64CuATSM better suited to identify compromised but salvageable myocardium, validated using parallel biomarkers of cardiac energetics comparable to those observed in chronic cardiac ischemic syndromes. Methods: Rat hearts were perfused with aerobic buffer for 20 min, followed by a range of hypoxic buffers (using a computer-controlled gas mixer) for 45 min. Contractility was monitored by intraventricular balloon, energetics by 31P NMR spectroscopy, lactate and creatine kinase release spectrophotometrically, and HIF1 by Western blotting. Results: We identify a key hypoxia threshold at a 30% buffer O2 saturation which induces a stable and potentially survivable functional and energetic compromise: LV developed pressure was depressed by 20%, and cardiac phosphocreatine was depleted by 65.5 ± 14% (p<0.05 vs control), but ATP levels were maintained. Lactate release was elevated (0.21 ± 0.067 versus 0.056 ± 0.01 mmol/L/min, p<0.05), but not maximal (0.46 ± 0.117 mmol/L/min), indicating residual oxidative metabolic capacity. HIF1 was elevated, but not maximal. At this key threshold, 64CuCTS selectively deposited significantly more 64Cu than any other tracer we examined (61.8 ± 9.6% injected dose versus 29.4 ± 9.5% for 64CuATSM p<0.05). Conclusion: The hypoxic threshold which induced survivable metabolic and functional compromise was 30% O2. At this threshold, only 64CuCTS delivered a hypoxic:normoxic contrast of 3:1, and it therefore warrants in vivo evaluation for imaging chronic cardiac ischemic syndromes.
    Journal of Nuclear Medicine 03/2015; DOI:10.2967/jnumed.114.148353 · 5.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Effective positron emission tomography / computed tomography (PET/CT) guidance in radiotherapy of lung cancer requires estimation and mitigation of errors due to respiratory motion. An end-to-end workflow was developed to measure patient-specific motion-induced uncertainties in imaging, treatment planning, and radiation delivery with respiratory motion phantoms and dosimeters. A custom torso phantom with inserts mimicking normal lung tissue and lung lesion was filled with [(18)F]FDG. The lung lesion insert was driven by six different patient-specific respiratory patterns or kept stationary. PET/CT images were acquired under motionless ground truth, tidal breathing motion-averaged (3D), and respiratory phase-correlated (4D) conditions. Target volumes were estimated by standardized uptake value (SUV) thresholds that accurately defined the ground-truth lesion volume. Non-uniform dose-painting plans using volumetrically modulated arc therapy were optimized for fixed normal lung and spinal cord objectives and variable PET-based target objectives. Resulting plans were delivered to a cylindrical diode array at rest, in motion on a platform driven by the same respiratory patterns (3D), or motion-compensated by a robotic couch with an infrared camera tracking system (4D). Errors were estimated relative to the static ground truth condition for mean target-to-background (T/Bmean) ratios, target volumes, planned equivalent uniform target doses, and 2%-2 mm gamma delivery passing rates. Relative to motionless ground truth conditions, PET/CT imaging errors were on the order of 10-20%, treatment planning errors were 5-10%, and treatment delivery errors were 5-30% without motion compensation. Errors from residual motion following compensation methods were reduced to 5-10% in PET/CT imaging, <5% in treatment planning, and <2% in treatment delivery. We have demonstrated that estimation of respiratory motion uncertainty and its propagation from PET/CT imaging to RT planning, and RT delivery under a dose painting paradigm is feasible within an integrated respiratory motion phantom workflow. For a limited set of cases, the magnitude of errors was comparable during PET/CT imaging and treatment delivery without motion compensation. Errors were moderately mitigated during PET/CT imaging and significantly mitigated during RT delivery with motion compensation. This dynamic motion phantom end-to-end workflow provides a method for quality assurance of 4D PET/CT-guided radiotherapy, including evaluation of respiratory motion compensation methods during imaging and treatment delivery.
    Physics in Medicine and Biology 04/2015; 60(9):3731-3746. DOI:10.1088/0031-9155/60/9/3731 · 2.92 Impact Factor