PET of HER2-Positive Pulmonary Metastases with ¹⁸F-Z_HER2:342 Affibody in a Murine Model of Breast Cancer: Comparison with ¹⁸F-FDG

Abstract

Targeted therapies often depend on the expression of the target present in the tumor. This expression can be difficult to ascertain in widespread metastases. 18 F-FDG PET/CT, although sensitive, is nonspecific for particular tumor markers. Here, we compare the use of a human epidermal growth factor receptor 2 (HER2)-specific 18 F-Z HER2:342 -Affibody and 18 F-FDG in HER2-expressing pulmonary metastases in a murine model of breast cancer. Methods: The lung metastasis model was established by intravenous injection of MDA-MB-231 HER2 -Luc human breast cancer cells into the tail vein. Bioluminescence imaging was used to evaluate metastasis progression. Uptake of 18 F-Z HER2:342 -Affibody and 18 F-FDG was confirmed by coregistration of the PET images with MR and CT images. At the end of the study, the presence of neoplastic cells and HER2 expression in lung tissues, and distribution of the tracer, were assessed ex vivo by immunohistochemistry and autoradiography. Results: 18 F-Z HER2:342 -Affibody successfully targeted HER2-positive lesions in the lung and allowed detection of metastases as early as 9 wk after injection of cells. In contrast, 18 F-FDG uptake was often masked by surrounding inflammatory changes and was nonspecific for HER2 expression. HER2 expression at a cellular level correlated well with tracer uptake on autoradiography. Conclusion: 18 F-Z HER2:342 -Affibody is a promising tracer for evaluation of HER2 status of breast cancer metastases and is more specific for detecting HER2-positive lesions than 18 F-FDG.

A review on segmentation of positron emission tomography images

“…Meanwhile, a large number of new compounds are also becoming prospects for PET imaging which have some advantages over FDG such as tracers that do not accumulate in the heart/kidney. However, FDG still remains the most commonly used radiotracer in the clinical routine for body imaging [15]. At the time of this writing, there is no reported study in the literature mimicking the differences of segmentation accuracy caused by using different radiotracers in PET imaging.…”

Three Methods for 18F Labeling of the HER2-Binding Affibody Molecule ZHER2:2891 Including Preclinical Assessment

“…Using the HercepTEST standard scoring scale (0 to 13), Figure 2A shows that NCI-N87 tumors stain strongly (13), whereas A431 cells show a considerably weaker staining intensity (11). In biodistribution studies, all radiolabeled Affibody molecules showed an increased retention in the high-HER2-expressing NCI-N87 tumors, compared with the low-HER2-expressing A431 tumors (Fig.…”

Positron Emission Tomography Imaging with 18F-Labeled ZHER2:2891 Affibody for Detection of HER2 Expression and Pharmacodynamic Response to HER2-Modulating Therapies

“…Affibody radiotracers have been developed to overcome the shortcomings of large (150 kDa) antibodies. To date, most of the reported studies of radiolabeled Affibodies in the literature have used analogs of Z HER2:342 labeled with radiometals or radiohalogens (17,(25)(26)(27)(28)(29)(30)(31). Recently, re-engineering of this Affibody by Feldwisch and colleagues (32) led to an optimized scaffold containing 11 amino acid substitutions in the nonbinding surface of the Affibody removing similarity to the original protein A domain-Z HER2:2891 .…”