Validation of simplified uptake measures against dynamic Patlak K(i) for quantification of lesional (89)Zr-Immuno-PET antibody uptake

PURPOSE: Positron emission tomography imaging of zirconium-89-labelled monoclonal antibodies ((89)Zr-Immuno-PET) allows for visualisation and quantification of antibody uptake in tumours in vivo. Patlak linearization provides distribution volume (V(T)) and nett influx rate (K(i)) values, representing reversible and irreversible uptake, respectively. Standardised uptake value (SUV) and tumour-to-plasma/tumour-to-blood ratio (TPR/TBR) are often used, but their validity depends on the comparability of plasma kinetics and clearances. This study assesses the validity of SUV, TPR and TBR against Patlak K(i) for quantifying irreversible (89)Zr-Immuno-PET uptake in tumours. METHODS: Ten patients received 37 MBq 10 mg (89)Zr-anti-EGFR with 500 mg/m(2) unlabelled mAbs. Five patients received two doses of 37 MBq (89)Zr-anti-HER3: 8–24 mg for the first administration and 24 mg–30 mg/kg for the second. Seven tumours from four patients showed (89)Zr-anti-EGFR uptake, and 18 tumours from five patients showed (89)Zr-anti-HER3 uptake. SUV(peak,) TPR(peak) and TBR(peak) values were obtained from one to six days p.i. Patlak linearization was applied to tumour time activity curves and plasma samples to obtain K(i). RESULTS: For (89)Zr-anti-EGFR, there was a small variability along the linear regression line between SUV (− 0.51–0.57), TPR (− 0.06‒0.11) and TBR (− 0.13‒0.16) on day 6 versus K(i). Similar doses of (89)Zr-anti-HER3 showed similar variability for SUV (− 1.3‒1.0), TPR (− 1.1‒0.53) and TBR (− 1.5‒0.72) on day 5 versus K(i). However, for the second administration of (89)Zr-anti-HER3 with a large variability in administered mass doses, SUV showed a larger variability (− 1.4‒2.3) along the regression line with K(i), which improved when using TPR (− 0.38–0.32) or TBR (− 0.56‒0.46). CONCLUSION: SUV, TPR and TBR at late time points were valid for quantifying irreversible lesional (89)Zr-Immuno-PET uptake when constant mass doses were administered. However, for variable mass doses, only TPR and TBR provided reliable values for irreversible uptake, but not SUV, because SUV does not take patient and mass dose-specific plasma clearance into account. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-023-06151-1.