111In-Benzyl-DTPA–ZHER2:342, an Affibody-Based Conjugate for In Vivo Imaging of HER2 Expression in Malignant Tumors

Data on expression of the HER2 (erbB-2) receptor in breast car-cinoma make it possible to select the most efficient treatment. There are strong indications that HER2 expression possesses prognostic and predictive values in ovarian, prostate, and lung carcinomasaswell. VisualizationofHER2expressionusing radio-nuclide targeting can provide important diagnostic information. The Affibody ZHER2:342 is a short (;7 kDa) phage-display– selected protein that binds HER2 with an affinity of 22 pmol/L. The goal of this study was to evaluate whether 111In-labeled HER2: 342 can be used for imaging of HER2 overexpression in vivo. Methods: ZHER2:342 was labeled with 111In via isothiocyanate-benzyl-DTPA (DTPA is diethylenetriaminepentaacetic acid) and the conjugate was characterized in vitro and in vivo. Results: 111In-Benzyl-DTPA–ZHER2:342 preserved the capacity to bind living HER2-expressing cells specifically. The affinity of In-benzyl-DTPA–ZHER2:342 to HER2 was 21 pmol/L according to surface plasmon resonance measurements. In nude mice bearing HER2-expressing SKOV-3 xenografts, a tumor uptake of 12 % 6 3 % injected activity per gram and a tumor-to-blood ratio of about 100 were obtained 4 h after injection. Tumor up-take in vivo was receptor specific, as it could be blocked with an excess of nonlabeled ZHER2:342. HER2-expressing xeno-grafts were clearly imaged 4 h after injection using a g-camera. Conclusion: 111In-Benzyl-DTPA–ZHER2:342 is a promising candi-date for visualization of HER2 expression in carcinomas, using the single-photon detection technique