Optimal definition of biological tumor volume using positron emission tomography in an animal model

Background: The goal of the study is to investigate ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET)’s ability to delineate the viable portion of a tumor in an animal model using cross-sectional histology as the validation standard. Methods: Syngeneic mammary tumors were grown in female Lewis rats. Macroscopic histological images of the transverse tumor sections were paired with their corresponding FDG micro-PET slices of the same cranial-caudal location to form 51 pairs of co-registered images. A binary classification system based on four FDG-PET tumor contouring methods was applied to each pair of images: threshold based on (1) percentage of maximum tumor voxel counts (C_max), (2) percentage of tumor peak voxel counts (C_peak), (3) multiples of liver mean voxel counts (C_liver) derived from PERCIST, and (4) an edge-detection-based automated contouring system. The sensitivity, which represented the percentage of viable tumor areas correctly delineated by the gross tumor area (GTA) generated from a particular tumor contouring method, and the ratio (expressed in percentage) of the overestimated areas of a gross tumor area (GTA_OE)/whole tumor areas on the macroscopic histology (WTA_H), which represented how much a particular GTA extended into the normal structures surrounding the primary tumor target, were calculated. Results: The receiver operating characteristic curves of all pairs of FDG-PET images have a mean area under the curve value of 0.934 (CI of 0.911–0.954), for representing how well each contouring method accurately delineated the viable tumor area. FDG-PET single value threshold tumor contouring based on 30 and 35 % of tumor C_max or C_peak and 6 × C_liver + 2 × SD achieved a sensitivity greater than 90 % with a GTA_OE/WTA_H ratio less than 10 %. Contouring based on 50 % of C_max or C_peak had a much lower sensitivity of 67.2–75.6 % with a GTA_OE/WTA_H ratio of 1.1–1.7 %. Automated edge detection was not reliable in this system. Conclusions: Single-value-threshold tumor contouring using ¹⁸F-FDG-PET is able to accurately delineate the viable portion of a tumor. 30 and 35 % of C_max, 30 and 35 % of C_peak, and 6 × C_liver + 2 × SD are three appropriate threshold values to delineate viable tumor volume in our animal model. The commonly used threshold value of 50 % of C_max or C_peak failed to detect one third of the viable tumor volume in our model.