Non-Invasive Monitoring of HER2 Expression in Breast Cancer Patients with 99mTc-Affibody SPECT/CT

Background: Non-invasive monitoring of human epidermal growth factor receptor 2 (HER2) status in malignant lesions of breast cancer patients has been established in clinical positron emission computed tomography (PET). Objectives: In this study, we try to evaluate the feasibility of Tc-99m-labeled affibody in monitoring HER2 expression for breast cancer patients using single-photon emission computed tomography (SPECT) apparatus fused with a conventional CT scanner (SPECT/CT). Patients and Methods: HER2 affibody with endogenous chelating site was recombinantly expressed and purified. Tc-99m was added to HER2 affibody at carboxyl-terminal cystein site specifically. Breast cancer patients were enrolled for whole-body SPECT/CT imaging following intravenous administration of Tc-99m-labeled HER2 affibody. Regions of interest were drawn manually over tumor sites and the normal surrounding muscle. The HER2 status of breast cancer lesions was determined by post-surgical immunohistochemistry, and correlated with the uptake of Tc-99m-labeled affibody as measured by SPECT. Results: Administration of Tc-99m-labeled HER2 affibody was well tolerated by all patients without noticeable adverse side effects. Tc-99m-labeled affibody SPECT imaging clearly visualized HER2 positive breast cancer lesions at approximately 1.5 and 4.5 hours after affibody treatment. The tumor to background (T/B) ratios of locally hot breast cancer lesions by HER2 imaging were closely related to post-surgical HER2 expression levels of cancer tissues by immunohistochemistry. When the tumor:muscle ratio exceeded 2.4 (cutoff value) in transverse imaging, the tumor lesion was considered to be HER2-positive arbitrarily. The diagnostic sensitivity of Tc-99m-labeled affibody SPECT/CT in identifying HER2 positive breast cancer was 80 percent (12/15), while the specificity and accuracy of Tc-99m-labeled affibody SPECT/CT were 60 percent (9/15) and 70 percent (21/30) respectively. In tumors with a diameter greater than 12 mm, the sensitivity of Tc-99m-labeled affibody SPECT/CT was 100 percent (12/12). Conclusion: Tc-99m-labeled affibody SPECT/CT may find utility in evaluating HER2 expression in breast cancer patients, and may provide new modality for guiding HER2 targeted therapy complementary to biopsy in breast cancer.