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

Abstract
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 nonspecific
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 (Ki).
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. Ki values of CD20-negative (0.43 μL/g/h and 0.92 μL/g/h) and CEAnegative
tumours (mdn = 1.97 μL/g/h, interquartile range (IQR) = 1.50–2.39) were higher than zero. Median Ki 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.