89Zr-labeled Bispecific T-cell Engager AMG 211 PET Shows AMG 211 Accumulation in CD3-rich Tissues and Clear, Heterogeneous Tumor Uptake

Purpose: Biodistribution of bispecific antibodies in patients is largely unknown. We therefore performed a feasibility study in nine patients with advanced gastrointestinal adenocarcinomas to explore AMG 211 biodistribution (also known as MEDI-565), a ~55 kDa bispecific T-cell engager directed against carcinoembryonic antigen on tumor cells and cluster of differentiation 3 (CD3) on T-cells. Methods:89Zr-labeled AMG 211 as tracer, was administered alone or with cold AMG 211, for positron emission tomography (PET) imaging before and/or during AMG 211 treatment. Results: Before AMG 211 treatment, the optimal imaging dose was 200 µg ⁸⁹Zr-AMG 211 + 1,800 µg cold AMG 211. At 3 hours the highest blood pool standardized uptake value (SUV)_mean was 4.0, and tracer serum half-life was 3.3 hour. CD3-mediated uptake was clearly observed in CD3-rich lymphoid tissues including spleen and bone marrow (SUV_mean 3.2 and 1.8, respectively), and the SUV_mean decreased more slowly than in other healthy tissues. ⁸⁹Zr-AMG 211 remained intact in plasma and was excreted predominantly via the kidneys in degraded forms. Of 43 visible tumor lesions, 37 were PET quantifiable, with a SUV_max of 4.0 (interquartile range 2.7 - 4.4) at 3 hours using the optimal imaging dose. The tracer uptake differed between tumor lesions 5-fold within and 9-fold between patients. During AMG 211 treatment tracer was present in the blood pool, while tumor lesions were not visualized, possibly reflecting target saturation. Conclusion: This first-in-human study shows high, specific ⁸⁹Zr-AMG 211 accumulation in CD3-rich lymphoid tissues, as well as a clear, inter- and intra-individual heterogeneous tumor uptake.

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