ORIGINAL ARTICLES  ADVANCES IN RADIOIMMUNOIMAGING AND RADIOIMMUNOTHERAPY 

The Quarterly Journal of Nuclear Medicine and Molecular Imaging 2007 December;51(4):314-23

Copyright © 2007 EDIZIONI MINERVA MEDICA

lingua: Inglese

Evaluation of [111/114mIn]CHX-A’’-DTPA-ZHER2:342, an Affibody ligand coniugate for targeting of HER2-expressing malignant tumors

Orlova A. ^{1, 2}, Rosik D. ¹, Sandström M. ³, Lundqvist H. ², Einarsson L. ⁴, Tolmachev V. ^{1, 2}

¹ Affibody AB, Bromma, Sweden 2 Division of Biomedical Radiation Sciences Uppsala University, Uppsala, Sweden 3 Department of Hospital Physics Uppsala University Hospital, Uppsala, Sweden 4 The Svedberg Laboratory Uppsala University, Uppsala, Sweden

Aim. Radionuclide imaging of the HER2 receptor, which is a target for trastuzumab therapy, can provide important diagnostic information. Further, targeting radionuclide therapy might be an option for treatment of HER2 expressing tumors. The phage-display selected Affibody ligand ZHER2:342, which binds to HER2 with an affinity of 22 pM, may here play an important role. The small size of the ZHER2:342, 7.5 kDa, enables quick tumor localization and fast blood clearance. Earlier, successful targeting of HER2-expressing xenografts using ZHER2:342 labeled using [111In]benzyl-DTPA was reported. By changing to the CHX-A”-DTPA chelator, the stability and labeling kinetics of the radiometal-ZHER2:342 conjugate can be improved. The aim of this study was to evaluate the labeling of the CHX-A”-DTPA-ZHER2:342 conjugate with 111In for diagnostic imaging and with 114mIn for locoregional radionuclide therapy.
Methods. The isothiocyanate derivative of CHX-A”-DTPA was coupled to ZHER2:342 in alkaline conditions at 37 °C. The conjugate was labeled with both 111In and 114mIn and evaluated in vitro and in vivo.
Results. Labeling with 111In and 114mIn provided >95% yield after 30 min at RT. Specific radioactivity was 0.5 and 12 MBq/nmol, for 114mIn and 111In, respectively. The radiolabeled conjugates demonstrated specific binding to HER2 expressing SKOV-3 cells. In mice bearing SKOV-3 xenografts, the tumor uptake of [111In]CHX-A”-DTPA-ZHER2:342 4 h postinjection was 10.3±3.6% IA/g and tumor-to-blood ratio about 190.
Conclusion. [111In]CHX-A”-DTPA-ZHER2:342 is a promising candidate for the visualization of HER2 expression in malignant tumors. Labeled with114mIn it could also be used for locoregional treatment of HER2 expressing tumors.