Page 88 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Chapter 4
ibritumomab tiuxetan was not influenced by simultaneous therapy with 90Y-ibritumomab tiuxetan. Pre-therapy scout scans with 89Zr-ibritumomab tiuxetan can therefore be used to predict biodistribution and dose-limiting organ during therapy. These results indicate that 89Zr-immuno-PET may guide safe individualized therapy by optimizing the radioimmunotherapy dose of 90Y-ibritumomab tiuxetan.
The standard treatment with a high amount of cold rituximab before anti- CD20 based RIT, also administered to the patients in the study of Rizvi et al., is common practice to enhance the therapeutic index for RIT. It is thought that the usage of excess unlabeled mAb before RIT may reduce toxicity, in particular bone marrow toxicity. Preloading with unlabeled mAb might prevent normal tissue toxicity by providing a more predictable biodistribution of 90Y-labeled mAb, decreasing clearance rates, and prolonging its circulation half-life. This preload is assumed to clear the peripheral blood of circulating CD20-positive B cells and enhance tumor targeting of the 90Y-labeled antibody to tumor cells. However, supportive data for this approach is limited. It is unclear whether the preload may block subsequently administered 90Y-labeled anti-CD20 antibody, which might impair therapeutic effects.
Muylle et al. performed a study with 89Zr-rituximab-PET to explore the influence of a preload with unlabeled rituximab in five patients with CD20-positive B-cell lymphoma, scheduled for subsequent RIT with 90Y-labeled rituximab (46). The aim of the study was to compare the distribution of 89Zr-rituximab without and with a preload of unlabeled rituximab (within the same patient) to assess the impact on tumor targeting and radiation dose of subsequent radioimmunotherapy with 90Y-labeled rituximab. PET scans were obtained at baseline after administration of 111 MBq 89Zr-labeled rituximab (10 mg). After 3 weeks, a standard preload of unlabeled rituximab (250 mg/m2) was administered, immediately followed by administration of 10 mg 89Zr-rituximab, and PET scans were acquired.
For the patients with B cell depletion (n=3) tumor uptake without a preload was consistently higher. In patients with preserved circulating B cells (n=2), 3 lesions showed less or no uptake without a preload, while other lesions showed higher uptake. The authors explain higher tumor uptake upon preload by improved biodistribution and prevention of sequestration of 89Zr-rituximab in the ‘antigen- sink’, consisting of CD20-positive B cells in the circulation and in the spleen. Impaired targeting of other tumor sites, however, is explained by partial saturation with unlabeled rituximab.
86