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¹¹¹In-Benzyl-DTPA–Z_HER2:342, an Affibody-Based Conjugate for In Vivo Imaging of HER2 Expression in Malignant Tumors

¹ Division of Biomedical Radiation Sciences, Uppsala University, Uppsala, Sweden; ² Affibody AB, Bromma, Sweden; and ³ Department of Hospital Physics, Uppsala University Hospital, Uppsala, Sweden

Correspondence: For correspondence or reprints contact: Vladimir Tolmachev, PhD, Division of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, S-751 85, Uppsala, Sweden. E-mail: vladimir.tolmachev{at}bms.uu.se

Data on expression of the HER2 (erbB-2) receptor in breast carcinoma 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 carcinomas as well. Visualization of HER2 expression using radionuclide targeting can provide important diagnostic information. The Affibody Z_HER2:342 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: Z_HER2:342 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–Z_HER2:342 preserved the capacity to bind living HER2-expressing cells specifically. The affinity of In-benzyl-DTPA–Z_HER2:342 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% ± 3% injected activity per gram and a tumor-to-blood ratio of about 100 were obtained 4 h after injection. Tumor uptake in vivo was receptor specific, as it could be blocked with an excess of nonlabeled Z_HER2:342. HER2-expressing xenografts were clearly imaged 4 h after injection using a -camera. Conclusion: ¹¹¹In-Benzyl-DTPA–Z_HER2:342 is a promising candidate for visualization of HER2 expression in carcinomas, using the single-photon detection technique.

Key Words: Affibody • HER2 • tumor targeting • ¹¹¹In • benzyl-DTPA

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