Page 183 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Towards 89Zr-immuno-PET to measure target engagement of antibodies
scanner (GE Healthcare, Waukesha, WI, USA). At Amsterdam UMC, PET scans were acquired on a Philips Gemini TF-64 or Ingenuity TF-128 PET/CT scanner (Philips Healthcare, Best, the Netherlands). For all procedures, a low dose computed tomography scan was used for attenuation and scatter correction. Volumes of interest (VOI) of the kidney, liver, lung and spleen were manually delineated on each scan and characterized by the mean radioactivity concentration in Bq×cm-3. All radioactivity concentrations were decay corrected to the time of injection.
For each antibody, the Human Protein Atlas (20) was used as reference for lack of target antigen expression in tissues of interest.
Patlak Linearization
Patlak linearization applied to multiple-time tissue activity concentration measurements allows an estimate of the reversible and the irreversible contributions to the measured activity. The method was initially applied to blood-to-brain transfer and considered the fate of a test solute to obtain transfer constants (14,21). For 89Zr-immuno-PET, we utilized this method to determine reversible and irreversible non-specific uptake of therapeutic antibodies. This analysis was performed per patient, for each tissue (liver, spleen, lung, kidney).
Input data consisted of the activity concentration in plasma (ACp in Bq×mL-1) and in tissue (ACt in Bq×cm-3) as a function of time post injection. The data were plotted as
with AC /AC along the y-axis and ∫AC (τ)dτ / AC along the x-axis (commonly 9 tppp
known as a ‘Patlak plot’).
The ∫AC (τ)dτ term represents the area under the plasma curve from the
p
time of injection up to the time of the measurement, and will be referred to as AUCp0-t. The offset of the Patlak plot represents the distribution volume VT (in mL×cm-3) and the slope of the Patlak plot, Ki (in mL×g-1×min-1), the net rate of irreversible uptake.
Late time points (defined as ≥ 1day p.i) were included in the linear fit, as equilibrium state was assumed for these time points (1). Early time points (scans at 1h p.i.) were therefore not included.
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