Interobserver reproducibility of tumor uptake quantification with 89Zr-immuno-PET: a multicenter analysis

PurposeIn-vivo quantification of tumor uptake of 89-zirconium (Zr-89)-labelled monoclonal antibodies (mAbs) with PET provides a potential tool in strategies to optimize tumor targeting and therapeutic efficacy. A specific challenge for Zr-89-immuno-PET is low tumor contrast. This is expected to result in interobserver variation in tumor delineation. Therefore, the aim of this study was to determine interobserver reproducibility of tumor uptake measures by tumor delineation on Zr-89-immuno-PET scans.MethodsData were obtained from previously published clinical studies performed with Zr-89-rituximab, Zr-89-cetuximab and Zr-89-trastuzumab. Tumor lesions on Zr-89-immuno-PET were identified as focal uptake exceeding local background by a nuclear medicine physician. Three observers independently manually delineated volumes of interest (VOI). Maximum, peak and mean standardized uptake values (SUVmax, SUVpeak and SUVmean) were used to quantify tumor uptake. Interobserver variability was expressed as the coefficient of variation (CoV). The performance of semi-automatic VOI delineation using 50% of background-corrected AC(peak) was described.ResultsIn total, 103 VOI were delineated (3-6days post injection (D3-D6)). Tumor uptake (median, interquartile range) was 9.2 (5.2-12.6), 6.9 (4.0-9.6) and 5.5 (3.3-7.8) for SUVmax, SUVpeak and SUVmean. Interobserver variability was 0% (0-12), 0% (0-2) and 7% (5-14), respectively (n=103). The success rate of the semi-automatic method was 45%. Inclusion of background was the main reason for failure of semi-automatic VOI.ConclusionsThis study shows that interobserver reproducibility of tumor uptake quantification on Zr-89-immuno-PET was excellent for SUVmax and SUVpeak using a standardized manual procedure for tumor segmentation. Semi-automatic delineation was not robust due to limited tumor contrast.