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

Moek, Kirsten L.; Waaijer, Stijn J.H.; Kok, Iris C.; Suurs, Frans V.; Brouwers, Adrienne H.; Menke-van der Houven van Oordt, C. Willemien; Wind, Thijs T.; Gietema, Jourik A.; Schröder, Carolien P.; Mahesh, Shekar V.K.; Jorritsma-Smit, Annelies; Lub-de Hooge, Marjolijn N.; Fehrmann, Rudolf S.N.; de Groot, Derk Jan A.; de Vries, Elisabeth G.E.

doi:10.1158/1078-0432.22470416.v1

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

journal contribution

posted on 2023-03-31, 20:48 authored by Kirsten L. Moek, Stijn J.H. Waaijer, Iris C. Kok, Frans V. Suurs, Adrienne H. Brouwers, C. Willemien Menke-van der Houven van Oordt, Thijs T. Wind, Jourik A. Gietema, Carolien P. Schröder, Shekar V.K. Mahesh, Annelies Jorritsma-Smit, Marjolijn N. Lub-de Hooge, Rudolf S.N. Fehrmann, Derk Jan A. de Groot, Elisabeth G.E. de Vries

Supplementary methods, Supplementary Fig. S1, Supplemtary Table S1, Supplementary Table S2, Supplementary Table S3

History

ARTICLE ABSTRACT

Biodistribution of bispecific antibodies in patients is largely unknown. We therefore performed a feasibility study in 9 patients with advanced gastrointestinal adenocarcinomas to explore AMG 211 biodistribution (also known as MEDI-565), an approximately 55 kDa bispecific T-cell engager (BiTE®) directed against carcinoembryonic antigen (CEA) on tumor cells and cluster of differentiation 3 (CD3) on T-cells. 89Zr-labeled AMG 211 as tracer was administered alone or with cold AMG 211, for PET imaging before and/or during AMG 211 treatment. 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 hours. CD3-mediated uptake was clearly observed in CD3-rich lymphoid tissues including spleen and bone marrow (SUVmean 3.2 and 1.8, respectively), and the SUVmean 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 SUVmax of 4.0 [interquartile range (IQR) 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, whereas tumor lesions were not visualized, possibly reflecting target saturation. This first-in-human study shows high, specific 89Zr-AMG 211 accumulation in CD3-rich lymphoid tissues, as well as a clear, inter- and intraindividual heterogeneous tumor uptake.