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

• Published in: Clinical cancer research Vol. 25; no. 12; p. 3517
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States 15-06-2019
• ISSN: 1078-0432

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.
Zr-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
Zr-AMG 211 + 1,800-μg cold AMG 211. At 3 hours, the highest blood pool standardized uptake value (SUV)
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 (SUV
3.2 and 1.8, respectively), and the SUV
decreased more slowly than in other healthy tissues.
Zr-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
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
Zr-AMG 211 accumulation in CD3-rich lymphoid tissues, as well as a clear, inter- and intraindividual heterogeneous tumor uptake.