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

In-vivo quantification of tumor uptake of 89-zirconium (⁸⁹Zr)-labelled monoclonal antibodies (mAbs) with PET provides a potential tool in strategies to optimize tumor targeting and therapeutic efficacy. A specific challenge for ⁸⁹Zr-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 ⁸⁹Zr-immuno-PET scans.

Data were obtained from previously published clinical studies performed with ⁸⁹Zr-rituximab, ⁸⁹Zr-cetuximab and ⁸⁹Zr-trastuzumab. Tumor lesions on ⁸⁹Zr-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.

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.

This study shows that interobserver reproducibility of tumor uptake quantification on ⁸⁹Zr-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.