P2-09-01: First-in-Human Whole-Body HER2−Receptor Mapping Using Affibody Molecular Imaging

Autor: Jörgen Carlsson, Henrik Lindman, U Garske, Joachim Feldwisch, Jens Nørkær Sørensen, Dan Sandberg, Anders Wennborg
Rok vydání: 2011
Předmět:
Zdroj: Cancer Research. 71:P2-09
ISSN: 1538-7445
0008-5472
DOI: 10.1158/0008-5472.sabcs11-p2-09-01
Popis: Background: ABY-025 is a member of a promising class of scaffold-based antibody alternatives known as Affibody molecules with superior properties for molecular imaging compared to monoclonal antibodies. It is a minimal-size, high-affinity HER2 binder, noncompetitive with trastuzumab allowing imaging even during trastuzumab therapy. This pilot clinical study set out to establish a safe clinical procedure for further tests and to verify whether breast cancer lesions could be identified and characterized for HER2 expression using single-photon emission computed tomography (SPECT) imaging. Patients and methods: Seven patients with metastatic breast cancer, five with HER2 positive primary tumors and two HER2 negative controls were included. A standard 3-hour 18F-FDG-PET was performed to locate the lesions and 5 days later an injection with 111Inlabeled ABY-025 was given followed by whole body scanning at 30 minutes with additional SPECT at 4, 24 and 48 hours. Biopsies were taken from amenable lesions and analyzed by immunohistochemistry to verify the HER2 status. Results: Large metastases were visualized already at 30 minutes and at later registrations a majority of all known lesions could be identified. A brain metastasis showed exceptionally high HER2 signal-to-background-ratio. Two fundamental behaviors were observed: High tumor to background ratio, increasing over time, was predominant in the HER2−positive group while the HER2−negative group generally presented a lower ratio. One patient in the positive group unexpectedly showed low tumor to background ratio similar to the negative group. Biopsy verified that the initially positive patient had converted to low HER2 expression. All other biopsies confirmed that the metastases were still positive or negative in line with the subject's primary lesions. None of the subjects had any adverse reactions due to the investigations. Conclusion: ABY-025 can be used safely in humans with similar excellent whole body HER2−receptor molecular imaging capabilities as have already been observed in animal models. Promising indications of in vivo HER2−receptor status discriminatory capabilities were observed. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-09-01.
Databáze: OpenAIRE
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