JNM: HER2-targeting affibody bests FDG for imaging pulmonary metastases

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Metastasis Growth in Mouse Breast Cancer Model - 123.95 Kb
BLI monitoring of metastasis growth. Representative in vivo images of lungs of mouse number two 10 wk after cell injection. Source: J Nucl Med doi: 10.2967/jnumed.111.100354

An affibody which targets human epidermal growth factor receptor 2 (HER2)-expressing breast cancer lesions has been shown to allow early detection of HER2-positive pulmonary metastases and with more specificity than 18F-FDG, according to a study published online May 11 in the Journal of Nuclear Medicine.

The affibody molecule 18F- Z(HER2:342) may lead to imaging that could aid in the identification and staging of breast cancer metastases, according to study authors Gabriela Kramer-Marek, PhD, of the National Cancer Institute at the National Institutes of Health in Bethesda, Md., and colleagues.

“Molecular imaging has the potential to provide noninvasive information about the receptor expression profile of tumors, which can aid in initial tumor characterization and in treatment selection and monitoring,” wrote the authors.

The authors explained that amplification or overexpression of HER2 is associated with aggressive tumors and has been detected in about 20 percent of invasive breast cancers. Treatment with the humanized monoclonal antibody, trastuzumab, has resulted in survival improvements for patients with HER2-positive lesions.

But there’s a catch. Kramer-Marek et al explained that HER2 status is currently determined by immunohistochemistry and fluorescence in situ hybridization at the time of diagnosis of the primary tumor, but high disparities in HER2 expression between primary and metachronous metastases has been reported. An accurate assessment of HER2 status could lead to more efficient treatment with trastuzumab.

18F-FDG frequently leads to false-positive findings when attempting to selectively identify HER2-positive tumors, mainly caused by inflammation, so the authors tested the effectiveness of the 18F-Z(HER2:342) affibody in an experimental breast cancer lung metastasis model created by intravenous injection of cancer cells in six week old female mice. Kramer-Marek recognized that such a method is flawed as a biologic model of metastases, but found it adequate for comparing imaging modalities in the detection of pulmonary nodules.

HER2-positive pulmonary nodules were visualized as early as nine weeks after injection of the tumor cells. Accurate measurements of uptake were available as early as one hour after injection. The data demonstrated less effectiveness on 18F-FDG imaging due to the fact that HER2-positive pulmonary metastases can be obscured by surrounding inflammation, according to the authors.

At the end of the study, lung tissues were assessed ex vivo and the authors were able to confirm the tracer’s ability to successfully target submillimeter foci of HER2-positive tumors using immunohistochemistry and autoradiography.

They also noted that the HER2 affibody resulted in high contrast between the tumor and other tissues due to the tracer’s small size, rapid clearance and high affinity of binding to HER2.

“Therefore, we believe that the high selectivity and specificity of [18F- Z(HER2:342)]-affibody is of potential interest in clinical situations in which the HER2 status of metastases needs to be reassessed during treatment,” wrote the authors.