Correlation of PET images of metabolism, proliferation and hypoxia to characterize tumor phenotype in patients with cancer of the oropharynx.
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.
University of Wisconsin, Madison 98195-6043, USA. nyflot@uw.edu
Matthew J
MJ
Nyflot
Paul M
PM
Harari
Stephen
S
Yip
Scott B
SB
Perlman
Robert
R
Jeraj
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000000981:diagnostic imaging; D015687:Cell Hypoxia; D049109:Cell Proliferation; D056831:Coordination Complexes; D015224:Dideoxynucleosides; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D009942:Organometallic Compounds; D009959:Oropharyngeal Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D012680:Sensitivity and Specificity; D013882:Thiosemicarbazones; D014057:Tomography, X-Ray Computed
D056831:Coordination Complexes; D015224:Dideoxynucleosides; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D013882:Thiosemicarbazones; C089548:copper (II) diacetyl-di(N(4)-methylthiosemicarbazone); D019788:Fluorodeoxyglucose F18