Non-Invasive Monitoring of HER2 Expression in Breast Cancer Patients with lt;sup gt;99m lt;/sup gt;Tc-Affibody SPECT/CT

Background]Noninvasive 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 sup 99m /sup Tclabeled affibody in monitoring HER2 expression for breast cancer patients using singlephoton 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. sup 99m /sup Tc was added to HER2 affibody at carboxylterminal cystein site specifically. Breast cancer patients were enrolled for wholebody SPECT/CT imaging following intravenous administration of sup 99m /sup Tclabeled 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 postsurgical immunohistochemistry, and correlated with the uptake of sup 99m /sup Tclabeled affibody as measured by SPECT.[Results]Administration of sup 99m /sup Tclabeled HER2 affibody was well tolerated by all patients without noticeable adverse side effects. sup 99m /sup Tclabeled 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 postsurgical 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 HER2positive arbitrarily. The diagnostic sensitivity of sup 99m /sup Tclabeled affibody SPECT/CT in identifying HER2 positive breast cancer was 80 percent (12/15), while the specificity and accuracy of sup 99m /sup Tclabeled 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 sup 99m /sup Tclabeled affibody SPECT/CT was 100 percent (12/12).[Conclusion] sup 99m /sup Tclabeled 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.