Non-specific irreversible ⁸⁹Zr-mAb uptake in tumours: evidence from biopsy-proven target-negative tumours using ⁸⁹Zr-immuno-PET

Background: Distribution of mAbs into tumour tissue may occur via different processes contributing differently to the ⁸⁹Zr-mAb uptake on PET. Target-specific binding in tumours is of main interest; however, non-specific irreversible uptake may also be present, which influences quantification. The aim was to investigate the presence of non-specific irreversible uptake in tumour tissue using Patlak linearization on ⁸⁹Zr-immuno-PET data of biopsy-proven target-negative tumours. Data of two studies, including target status obtained from biopsies, were retrospectively analysed, and Patlak linearization provided the net rate of irreversible uptake (K_i). Results: Two tumours were classified as CD20-negative and two as CD20-positive. Four tumours were classified as CEA-negative and nine as CEA-positive. K_i values of CD20-negative (0.43 µL/g/h and 0.92 µL/g/h) and CEA-negative tumours (mdn = 1.97 µL/g/h, interquartile range (IQR) = 1.50–2.39) were higher than zero. Median K_i values of target-negative tumours were lower than CD20-positive (1.87 µL/g/h and 1.90 µL/g/h) and CEA-positive tumours (mdn = 2.77 µL/g/h, IQR = 2.11–3.65). Conclusion: Biopsy-proven target-negative tumours showed irreversible uptake of ⁸⁹Zr-mAbs measured in vivo using ⁸⁹Zr-immuno-PET data, which suggests the presence of non-specific irreversible uptake in tumours. Consequently, for ⁸⁹Zr-immuno-PET, even if the target is absent, a tumour-to-plasma ratio always increases over time.