Accuracy of a dual day scan protocol to estimate the radiation dose of ⁸⁹Zr-labeled monoclonal antibodies

Objectives Radiation dose estimates of ⁸⁹Zr-labeled monoclonal antibodies (mAbs) are based on their biodistribution as a function of time. It is common practice to measure the biodistribution at least 3 times, with an early scan acquired immediately after injection. The aim of this study was to investigate the accuracy of radiation dose estimates based on a dual day (2D) scan protocol, leaving out the early scan.

Methods Dosimetry data were acquired in clinical studies on ⁸⁹Zr-Rituximab (Rtx, n=4), ⁸⁹Zr-Cetuximab (Ctx, n=5) and ⁸⁹Zr-X (experimental mAb, n=5), including an early scan at 1-2hrs post injection (p.i.) and two scans in the range of 1 to 6 days p.i.. For each scan, whole body (WB) as well as organ uptake in percent injected dose (%ID) were derived. Effective residence time estimates were obtained for whole body (τ_WB) and a number of organs (τ_organ; kidney, liver, lung, spleen and red marrow). OLINDA (1) was used to derive effectiveradiation dose estimates E (in mSv/MBq). A 2D scan protocol requires a value for the WB %ID from a hypothetical early scan (%ID_WB,h; taken to be the average of the measured values of all 14 patients). In addition, the %ID for the WB at the first and second scan day (%ID_WB,1 and %ID_WB,2), as well as the %ID for the WB and the organs, averaged over the first and second scan (%ID_WB,avg and %ID_organ,avg) were derived. This allowed for calculation of τ_WB,2D as well as τ_organ,2D = %ID_{organ, avg} / %ID_{WB, avg} x τ_WB,2D. From these values, E_2D was calculated.

Results τ_WB values were 97.7 ± 7.8, 98.0 ± 7.4 and 87.8 ± 3.0 h for Rtx, Ctx and X. Average E values per mAb were 0.54 ± 0.08, 0.53 ± 0.09 and 0.51 ± 0.04 mSv/MBq, respectively. From the early scans, %ID_WB,h was found to be 86 ± 4 % at 1.6 ± 0.6 h. For Rtx, Ctx and X, τ_WB,2D estimates deviated 2 ± 1, 3 ± 1 and 6 ± 3%, from the estimates based on all scans. Corresponding average deviations for E_2D were 2 ± 1, 3 ± 1 and 6 ± 3 % (up to + 10% on a per patient level).

Conclusions These results indicate that a dual day scan protocol, leaving out the early scan, can be used to obtain radiation dose estimate of a ⁸⁹Zr-mAb, with a maximum overestimation of ~10% per patient.