Impact of injected dose on accuracy and precision of tumor and organ uptake quantification of ⁸⁹Zr-labeled anti-CD20 antibodies with PET

Objectives Immuno-positron emission tomography (immuno-PET) enables visualization and quantification of tumor uptake and biodistribution of ⁸⁹Zirconium(⁸⁹Zr)-labeled monoclonal antibodies. The aim of this study was to assess accuracy and precision of tumor and organ quantification for an injected dose (ID) ranging from 18 to 74 MBq of ⁸⁹Zr-anti-CD20 antibodies, based on data acquired with an ID of 74 MBq.

Methods Whole body PET scans were obtained at 3 and 6 days post injection (p.i.) of 74 MBq ⁸⁹Zr-anti-CD20 antibodies in five patients with non-Hodgkin lymphoma. Organ (liver, spleen, lung and kidney) and tumor volumes of interest (VOIs) were delineated on all images. Mean activity concentrations (ACmean) and standard deviations (SD) were directly derived from these VOIs. Original PET list mode data were split in two and four sets, simulating scans as if obtained after injection of 37 and 18 MBq respectively. To assess accuracy and precision of quantification, Bland-Altman (BA) analyses were performed using averaged values of the 37 MBq sets, as well as the 18 MBq sets, compared to original 74 MBq data. Based on visual assessment of the BA plots, values of all organs for all timepoints were combined, as well as tumors for all timepoints. Mean percentage differences (limits of agreement) of ACmean and SD are presented.

Results All immuno-PET scans were obtained according to protocol, except for patient 2 at 6 days p.i. in whom only a partial scan could be obtained. Between the two sets of 37 MBq scans, as well as the four sets of 18 MBq scans, no significant differences were detected. The mean percentage differences for ACmean for tumors (n=51) and organs (n=32) were within 0.6%(-4 to 5%) for 37 MBq, and within 2% (-16 to 12%) for 18 MBq compared to 74 MBq data. SD values increased up to 13% (-24 to 7.1%) for 37 MBq and 34% (-60.6 to 6.6%) for 18 MBq.

Conclusions The consistent accuracy of tumor and organ quantification of ⁸⁹Zr-anti-CD20 supports an ID reduction from 74 to18 MBq, reducing radiation exposure for patients. Whether the corresponding decrease in precision is acceptable depends on the magnitude of expected clinically relevant differences in uptake.