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

Background: PET scans using zirconium-89 labelled monoclonal antibodies (⁸⁹Zr-mAbs), known as ⁸⁹Zr-immuno-PET, are made to measure uptake in tumour and organ tissue. Uptake is related to the supply of ⁸⁹Zr-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 ⁸⁹Zr-immuno-PET scans.

Methods: PET imaging and blood sampling of two ⁸⁹Zr-mAbs were included, ⁸⁹Zr-cetuximab and ⁸⁹Zr-durvalumab. For seven patients receiving ⁸⁹Zr-cetuximab, PET scans on 1-2 h, 2 and 6 days post-injection (p.i.) were analysed. Five patients received three injections of ⁸⁹Zr-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 ⁸⁹Zr-cetuximab and ⁸⁹Zr-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 ⁸⁹Zr-cetuximab and ⁸⁹Zr-durvalumab, respectively.

Conclusions: Image-derived blood concentrations should be obtained from delineating the ascending aorta in ⁸⁹Zr-immuno-PET scans, as this results in the lowest variability with respect to sample-derived blood concentrations.