Multicenter clinical trials using 18F-FDG PET to measure early oncology therapy response: Effects of injection-to-acquisition time variability on required sample size

摘要

Uptake time (duration between tracer injection and image acquisition) affects the standardized uptake value (SUV) measured for tumors in ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) images. With dissimilar uptake times, changes in tumor SUVs will be under- or overestimated. This study examines the influence of uptake time on tumor response assessment, using a virtual clinical trials approach.MethodsTumor kinetic parameters were estimated from dynamic ¹⁸F-FDG PET scans of breast cancer patients and used to simulate time-activity curves (TACs) for 45–120 minutes post-injection. Five-minute uptake time frames followed four scenarios: (#1) standardized static measurement time (60–65 minutes for all), (#2) uptake times sampled from an academic PET facility with strict adherence to standardization protocols, (#3) distribution similar to #2 but with greater deviation from standards, (#4) mixture of hurried scans (45–65 minute start of image acquisition) and frequent delays (58–115 minute uptake time). The proportion of out-of-range scans (<50 or >70 minutes, or >15 minutes difference between paired scans) was 0%, 20%, 44%, and 64% for scenarios #1, #2, #3, and #4. A published SUV correction based on local linearity of uptake time dependence was applied in a separate analysis. Influence of uptake time variation was assessed as sensitivity for detecting response (probability of observing a change of ≥30% decrease in ¹⁸F-FDG PET SUV, given a true decrease of 40%) and specificity (probability of observing absolute change of <30%, given no true change).