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Background: PET scans using zirconium-89 labelled monoclonal antibodies ( 89 Zr-mAbs), known as 89 Zr-immuno-PET, are made to measure uptake in tumour and organ tissue. Uptake is related to the supply of 89 Zr-mAbs in the blood. Measuring activity concentrations in blood, however, requires invasive blood sampling. This study aims to identify the best delineation strategy to obtain the image-derived blood concentration (IDBC) from 89 Zr-immuno-PET scans., Methods: PET imaging and blood sampling of two 89 Zr-mAbs were included, 89 Zr-cetuximab and 89 Zr-durvalumab. For seven patients receiving 89 Zr-cetuximab, PET scans on 1-2 h, 2 and 6 days post-injection (p.i.) were analysed. Five patients received three injections of 89 Zr-durvalumab. The scanning protocol for the first two injections consisted of PET scanning on 2, 5 and 7 days p.i. and for the third injection only on 7 days p.i. Blood samples were drawn with every PET scan and the sample-derived blood concentration (SDBC) was used as gold standard for the IDBC. According to an in-house developed standard operating procedure, the aortic arch, ascending aorta, descending aorta and left ventricle were delineated. Bland-Altman analyses were performed to assess the bias (mean difference) and variability (1.96 times the standard deviation of the differences) between IDBC and SDBC., Results: Overall, the activity concentration obtained from the IDBC was lower than from the SDBC. When comparing IDBC with SDBC, variability was smallest for the ascending aorta (20.3% and 17.0% for 89 Zr-cetuximab and 89 Zr-durvalumab, respectively). Variability for the other regions ranged between 17.9 and 30.8%. Bias for the ascending aorta was - 10.9% and - 11.4% for 89 Zr-cetuximab and 89 Zr-durvalumab, respectively., Conclusions: Image-derived blood concentrations should be obtained from delineating the ascending aorta in 89 Zr-immuno-PET scans, as this results in the lowest variability with respect to sample-derived blood concentrations., (© 2024. The Author(s).)

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., (© 2023. The Author(s).)