RT Journal Article
SR Electronic
T1 111In-Benzyl-DTPA–ZHER2:342, an Affibody-Based Conjugate for In Vivo Imaging of HER2 Expression in Malignant Tumors
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 846
OP 853
VO 47
IS 5
A1 Tolmachev, Vladimir
A1 Nilsson, Fredrik Y.
A1 Widström, Charles
A1 Andersson, Karl
A1 Rosik, Daniel
A1 Gedda, Lars
A1 Wennborg, Anders
A1 Orlova, Anna
YR 2006
UL http://jnm.snmjournals.org/content/47/5/846.abstract
AB 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 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% ± 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 ZHER2:342. HER2-expressing xenografts were clearly imaged 4 h after injection using a γ-camera. Conclusion: 111In-Benzyl-DTPA–ZHER2:342 is a promising candidate for visualization of HER2 expression in carcinomas, using the single-photon detection technique.