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

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. / 89Zr-labeled bispecific T-cell engager AMG 211 PET shows AMG 211 accumulation in CD3-rich tissues and clear, heterogeneous tumor uptake. In: Clinical Cancer Research. 2019 ; Vol. 25, No. 12. pp. 3517-3527.
@article{67f41958cea5433fa6968593537dc39e,
title = "89Zr-labeled bispecific T-cell engager AMG 211 PET shows AMG 211 accumulation in CD3-rich tissues and clear, heterogeneous tumor uptake",
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{\circledR}) 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.",
author = "Moek, {Kirsten L.} and Waaijer, {Stijn J. H.} and Kok, {Iris C.} and Suurs, {Frans V.} and Brouwers, {Adrienne H.} and {Menke-van der Houven van Oordt}, {C. Willemien} and Wind, {Thijs T.} and Gietema, {Jourik A.} and Schr{\"o}der, {Carolien P.} and Mahesh, {Shekar V. K.} and Annelies Jorritsma-Smit and {Lub-de Hooge}, {Marjolijn N.} and Fehrmann, {Rudolf S. N.} and {de Groot}, {Derk Jan A.} and {de Vries}, {Elisabeth G. E.}",
year = "2019",
doi = "10.1158/1078-0432.CCR-18-2918",
language = "English",
volume = "25",
pages = "3517--3527",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "12",

}

Moek, KL, Waaijer, SJH, Kok, IC, Suurs, FV, Brouwers, AH, Menke-van der Houven van Oordt, CW, Wind, TT, Gietema, JA, Schröder, CP, Mahesh, SVK, Jorritsma-Smit, A, Lub-de Hooge, MN, Fehrmann, RSN, de Groot, DJA & de Vries, EGE 2019, '89Zr-labeled bispecific T-cell engager AMG 211 PET shows AMG 211 accumulation in CD3-rich tissues and clear, heterogeneous tumor uptake' Clinical Cancer Research, vol. 25, no. 12, pp. 3517-3527. https://doi.org/10.1158/1078-0432.CCR-18-2918

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.

In: Clinical Cancer Research, Vol. 25, No. 12, 2019, p. 3517-3527.

Research output: Contribution to journalArticleAcademicpeer-review

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 - 10.1158/1078-0432.CCR-18-2918

DO - 10.1158/1078-0432.CCR-18-2918

M3 - Article

VL - 25

SP - 3517

EP - 3527

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 12

ER -