Evaluation of [(111/114m)In]CHX-A''-DTPA-ZHER2:342, an affibody ligand coniugate for targeting of HER2-expressing malignant tumors
2007 (English)In: The Quarterly Journal of Nuclear Medicine and Molecular Imaging, ISSN 1824-4785, Vol. 51, no 4, 314-323 p.Article in journal (Refereed) Published
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 Z(HER2:342), which binds to HER2 with an affinity of 22 pM, may here play an important role. The small size of the Z(HER2:342), 7.5 kDa, enables quick tumor localization and fast blood clearance. Earlier, successful targeting of HER2-expressing xenografts using Z(HER2:342) labeled using [(111)In]benzyl-DTPA was reported. By changing to the CHX-A''-DTPA chelator, the stability and labeling kinetics of the radiometal-Z(HER2:342) conjugate can be improved. The aim of this study was to evaluate the labeling of the CHX-A''-DTPA-Z(HER2:342) conjugate with (111)In for diagnostic imaging and with (114m)In for locoregional radionuclide therapy. METHODS: The isothiocyanate derivative of CHX-A''-DTPA was coupled to Z(HER2:342) in alkaline conditions at 37 degrees C. The conjugate was labeled with both (111)In and (114m)In and evaluated in vitro and in vivo. RESULTS: Labeling with (111)In and (114m)In provided >95% yield after 30 min at RT. Specific radioactivity was 0.5 and 12 MBq/nmol, for (114m)In and (111)In, respectively. The radiolabeled conjugates demonstrated specific binding to HER2 expressing SKOV-3 cells. In mice bearing SKOV-3 xenografts, the tumor uptake of [(111)In]CHX-A''-DTPA-Z(HER2:342) 4 h postinjection was 10.3+/-3.6% IA/g and tumor-to-blood ratio about 190. CONCLUSION: [(111)In]CHX-A''-DTPA-Z(HER2:342) is a promising candidate for the visualization of HER2 expression in malignant tumors. Labeled with (114m)In it could also be used for locoregional treatment of HER2 expressing tumors.
Place, publisher, year, edition, pages
2007. Vol. 51, no 4, 314-323 p.
Animals, Antibodies; Monoclonal/*pharmacokinetics/*therapeutic use, Cell Survival/radiation effects, Female, Ligands, Metabolic Clearance Rate, Mice, Organ Specificity, Ovarian Neoplasms/*metabolism/radionuclide imaging/*radiotherapy, Pentetic Acid/*analogs & derivatives/chemistry/diagnostic use/pharmacokinetics, Radiopharmaceuticals/chemical synthesis/diagnostic use/pharmacokinetics, Radiotherapy/*methods, Receptor; erbB-2/*metabolism, Recombinant Fusion Proteins/chemistry/*diagnostic use/*pharmacokinetics, Tissue Distribution, Treatment Outcome
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-17046ISI: 000252467900006PubMedID: 17464277OAI: oai:DiVA.org:uu-17046DiVA: diva2:44817