Phase III Open Label Trial for Use of [18F]-Fluoro-Deoxy-Glucose (18F-FDG) in Positron Emission Tomography Imaging in Oncology

1.0 Background & Introduction

In general, diagnostic imaging can address two issues: structure and function. One can either view structures in the body and image anatomy using structural imaging modalities such as plain film radiography (X-ray), Computerized Tomography (CT) and Magnetic Resonance Imaging (MRI), or one can view chemical processes and image biochemistry and function using biochemical imaging modalities such as Planar and Single Photon Emission Computerized Tomography (SPECT) imaging and Positron Emission Tomography (PET). The strength of the biochemical imaging methods is in distinguishing tissues according to metabolism rather than structure.

18F-Fluorodeoxyglucose (FDG) is the most commonly used tracer for PET imaging; its use and safety are well established world wide. The 18F-FDG is injected intravenously and is transported from blood to tissues in a manner similar to glucose. It has been understood for over 50 years, that cancer cells, in general, have increased glucose uptake and anaerobic metabolism compared to normal tissues. Like glucose, FDG is taken up into cells through glucose transport proteins (GLUT) and then phosphorylated by hexokinase to FDG-6-phosphate. However, since FDG-6-phosphate is not a substrate for subsequent glucose metabolic pathways and has a very low membrane permeability, the FDG-6-phosphate becomes trapped in tissue in proportion to the rate of glycolysis. This accumulation of 18F-FDG-6-phosphate forms the basis of tumor metabolic imaging with PET.

2.0 Indications

Cancer treatment and outcome depend largely on the accurate diagnosis and staging of disease. There is extensive data in the literature indicating the importance of PET imaging in accurately characterizing disease, determining stage and sites of recurrent disease in many cancer types. For these indications, it is well documented in the literature that functional imaging with PET exceeds sensitivity, specificity and accuracy of conventional 3-D imaging modalities. The most widely cited reference for the efficacy of PET imaging is: A Tabulated Summary of the FDG PET Literature, published by Gambhir et al, JNM (2001) 42: 1S-93S. In this study the average FDG PET sensitivity and specificity across all oncology applications are estimated at 84% (based on 18,402 patient studies) and 88% (based on 14,264 patient studies), respectively. The average management change across all applications is estimated to be 30% (based on 5,062 patients). Data was obtained combining 419 total articles and abstracts on studies in which FDG PET was used. Various methods of analysis were applied to these data, which revealed only a small amount of variation in the ratio values. Specifically, the sensitivity of PET ranged from 84 - 87%, the specificity ranged from 88% - 93%, and the accuracy ranged from 87 - 90%.