How to obtain the image-derived blood concentration from 89 Zr-immuno-PET scans

PET scans using zirconium-89 labelled monoclonal antibodies ( Zr-mAbs), known as Zr-immuno-PET, are made to measure uptake in tumour and organ tissue. Uptake is related to the supply of 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 Zr-immuno-PET scans. PET imaging and blood sampling of two Zr-mAbs were included, Zr-cetuximab and Zr-durvalumab. For seven patients receiving Zr-cetuximab, PET scans on 1-2 h, 2 and 6 days post-injection (p.i.) were analysed. Five patients received three injections of 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. 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 Zr-cetuximab and 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 Zr-cetuximab and Zr-durvalumab, respectively. Image-derived blood concentrations should be obtained from delineating the ascending aorta in Zr-immuno-PET scans, as this results in the lowest variability with respect to sample-derived blood concentrations.