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

Purpose In-vivo quantification of tumor uptake of 89-zirconium ( 89 Zr)-labelled monoclonal antibodies (mAbs) with PET provides a potential tool in strategies to optimize tumor targeting and therapeutic efficacy. A specific challenge for 89 Zr-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 89 Zr-immuno-PET scans. Methods Data were obtained from previously published clinical studies performed with 89 Zr-rituximab, 89 Zr-cetuximab and 89 Zr-trastuzumab. Tumor lesions on 89 Zr-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 (SUV max , SUV peak and SUV mean ) 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. Results In total, 103 VOI were delineated (3–6 days 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 SUV max , SUV peak and SUV mean. 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. Conclusions This study shows that interobserver reproducibility of tumor uptake quantification on 89 Zr-immuno-PET was excellent for SUV max and SUV peak using a standardized manual procedure for tumor segmentation. Semi-automatic delineation was not robust due to limited tumor contrast.