Page 87 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Initial clinical trials with 89Zr-immuno-PET in oncology
received a total protein dose of 10 mg mAb, administered as a co-infusion. The biological half-life of 89Zr-anti-MSLN in cohort 1 was shorter than in cohort 2, most likely due to faster antibody clearance related to small amounts of shed MSLN antigen present in the circulation. Bioavailability of the imaging dose in the second cohort was considered sufficient to evaluate tumor uptake.
This was the first study aiming the use of 89Zr-immuno-PET as an imaging
biomarker for whole body target expression and organs at risk for toxicity, to
ultimately guide dosing, confirm delivery, and predict efficacy of the ADC. At this
stage of development, however, 89Zr-immuno-PET was not able yet to add valuable information for individualized treatment decisions. 4
89Zr-labeled anti-CD20 mAbs in B cell lymphoma
Especially when using mAbs for radioimmunotherapy (RIT), 89Zr-immuno-PET may be applied to predict toxicity by assessment of biodistribution. This information may enable individualized treatment by optimizing dose schedules to limit unnecessary toxicity for patients.
RIT is used in the treatment of lymphoma, as this type of cancer is highly radiosensitive. More than 90% of B-cell non-Hodgkin lymphoma (NHL) express CD20, making it an attractive target for treatment. The transmembrane phosphoprotein CD20 is also expressed on mature B cells. The biological function of CD20 is still unclear. CD20 is highly expressed on the cell surface and is not rapidly internalized after antibody binding. The anti-CD20 antibody rituximab is widely used in both first-line, as well as subsequent treatment lines for patients with B-cell NHL. Anti-CD20 based RIT with yttrium-90 (90Y)-labeled- ibritumomab tiuxetan is currently approved for treatment of relapsed and refractory NHL (44). Bone marrow toxicity of RIT is dose-limiting, and especially patients with bone marrow infiltration may suffer excessive hematotoxicity.
Rizvi et al. published a clinical study on 89Zr-immuno-PET to predict toxicity of RIT in NHL patients in order to guide individualized dose optimization (45). The aim of this study was to assess whether pre-therapy scout scans with 89Zr- ibritumomab tiuxetan can be used to predict biodistribution of 90Y-ibritumomab tiuxetan and the dose limiting organ during therapy. Patients received standard treatment of 250 mg/m2 rituximab 1 week before and on the same day prior to both 90Y-and/or 89Zr-ibritumomab tiuxetan (70 MBq) administrations. The correlation between predicted pre-therapy and therapy organ absorbed doses as based on 89Zr-ibritumomab tiuxetan images was high. Biodistribution of 89Zr-
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