89Zr-labeled bispecific T-cell engager AMG 211 PET shows AMG 211 accumulation in CD3-rich tissues and clear, heterogeneous tumor uptake

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

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Purpose: 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. Experimental Design: 89Zr-labeled AMG 211 as tracer was administered alone or with cold AMG 211, for PET imaging before and/or during AMG 211 treatment. Results: Before AMG 211 treatment, the optimal imaging dose was 200-mg 89Zr-AMG 211 + 1,800-mg 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. Conclusions: 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.
Original languageEnglish
Pages (from-to)3517-3527
JournalClinical Cancer Research
Volume25
Issue number12
DOIs
Publication statusPublished - 2019

Cite this