TY - JOUR
T1 - 89Zr-labeled bispecific T-cell engager AMG 211 PET shows AMG 211 accumulation in CD3-rich tissues and clear, heterogeneous tumor uptake
AU - Moek, Kirsten L.
AU - Waaijer, Stijn J. H.
AU - Kok, Iris C.
AU - Suurs, Frans V.
AU - Brouwers, Adrienne H.
AU - Menke-van der Houven van Oordt, C. Willemien
AU - Wind, Thijs T.
AU - Gietema, Jourik A.
AU - Schröder, Carolien P.
AU - Mahesh, Shekar V. K.
AU - Jorritsma-Smit, Annelies
AU - Lub-de Hooge, Marjolijn N.
AU - Fehrmann, Rudolf S. N.
AU - de Groot, Derk Jan A.
AU - de Vries, Elisabeth G. E.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85066253736&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30745297
U2 - https://doi.org/10.1158/1078-0432.CCR-18-2918
DO - https://doi.org/10.1158/1078-0432.CCR-18-2918
M3 - Article
C2 - 30745297
SN - 1078-0432
VL - 25
SP - 3517
EP - 3527
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 12
ER -