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MAbs. 2014 Jul-Aug;6(4):1051-8. doi: 10.4161/mabs.29097. Epub 2014 May 7.

ImmunoPET and biodistribution with human epidermal growth factor receptor 3 targeting antibody ⁸⁹Zr-RG7116.

Author information

1
Department of Medical Oncology; University of Groningen; Groningen, The Netherlands; Department of Hospital and Clinical Pharmacy; University of Groningen; Groningen, The Netherlands.
2
Department of Hospital and Clinical Pharmacy; University of Groningen; Groningen, The Netherlands; Department of Nuclear Medicine and Molecular Imaging; University of Groningen; Groningen, The Netherlands.
3
Pharma Research & Early Development (pRED); F. Hoffmann-La Roche AG; Basel, Switzerland.
4
Department of Medical Oncology; University of Groningen; Groningen, The Netherlands.
5
Pharma Research & Early Development (pRED); Roche Diagnostics GmbH; Penzberg, Germany.
6
Department of Hospital and Clinical Pharmacy; University of Groningen; Groningen, The Netherlands.

Abstract

The humanized monoclonal antibody with high affinity for the human epidermal growth factor receptor (HER) 3, RG7116, is a glycoengineered, IgG1 class antibody. By labeling RG7116 with zirconium-89 ((89)Zr) we aimed to visualize in vivo HER3 expression and study the biodistribution of this antibody in human tumor-bearing mice. Biodistribution of (89)Zr-RG7116 was studied in subcutaneously xenografted FaDu tumor cells (HER3-positive). Dose-dependency of (89)Zr-RG7116 organ distribution and specific tumor uptake was assessed by administering doses ranging from 0.05 to 10 mg/kg RG7116 to SCID/Beige mice. Biodistribution was analyzed at 24 and 144 h after injection. MicroPET imaging was performed at 1, 3, and 6 days after injection of 1.0 mg/kg (89)Zr-RG7116 in the FaDu, H441, QG-56 and Calu-1 xenografts with varying HER3 expression. The excised tumors were analyzed for HER3 expression. Biodistribution analyses showed a dose- and time-dependent (89)Zr-RG7116 tumor uptake in FaDu tumors. The highest tumor uptake of (89)Zr-RG7116 was observed in the 0.05 mg/kg dose group with 27.5%ID/g at 144 h after tracer injection. MicroPET imaging revealed specific tumor uptake of (89)Zr-RG7116 in FaDu and H441 models with an increase in tumor uptake over time. Biodistribution data was consistent with the microPET findings in FaDu, H441, QG56 and Calu-1 xenografts, which correlated with HER3 expression levels. In conclusion, (89)Zr-RG7116 specifically accumulates in HER3 expressing tumors. PET imaging with this tracer provides real-time non-invasive information about RG7116 distribution, tumor targeting and tumor HER3 expression levels.

KEYWORDS:

89Zr; HER3; imaging; immunoPET; mAbs

PMID:
24870719
PMCID:
PMC4171008
DOI:
10.4161/mabs.29097
[Indexed for MEDLINE]
Free PMC Article

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