HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

Affibody-mediated tumour targeting of HER-2 expressing xenografts in mice.

AbstractPURPOSE:
Targeted delivery of radionuclides for diagnostic and therapeutic applications has until recently largely been limited to receptor ligands, antibodies and antibody-derived molecules. Here, we present a new type of molecule, a 15-kDa bivalent affibody called (Z(HER2:4))(2), with potential for such applications. The (Z(HER2:4))(2) affibody showed high apparent affinity (K (D)=3 nM) towards the oncogene product HER-2 (also called p185/neu or c-erbB-2), which is often overexpressed in breast and ovarian cancers. The purpose of this study was to investigate the in vivo properties of the new targeting agent.
METHODS:
The biodistribution and tumour uptake of the radioiodinated (Z(HER2:4))(2) affibody was studied in nude mice carrying tumours from xenografted HER-2 overexpressing SKOV-3 cells.
RESULTS:
The radioiodinated (Z(HER2:4))(2) affibody was primarily excreted through the kidneys, and significant amounts of radioactivity were specifically targeted to the tumours. The blood-borne radioactivity was, at all times, mainly in the macromolecular fraction. A tumour-to-blood ratio of about 10:1 was obtained 8 h post injection, and the tumours could be easily visualised with a gamma camera at this time point.
CONCLUSION:
The results indicate that the (Z(HER2:4))(2) affibody is an interesting candidate for applications in nuclear medicine, such as radionuclide-based tumour imaging and therapy.
AuthorsAnn-Charlott Steffen, Anna Orlova, Maria Wikman, Fredrik Y Nilsson, Stefan Ståhl, Gregory P Adams, Vladimir Tolmachev, Jörgen Carlsson
JournalEuropean journal of nuclear medicine and molecular imaging (Eur J Nucl Med Mol Imaging) Vol. 33 Issue 6 Pg. 631-8 (Jun 2006) ISSN: 1619-7070 [Print] Germany
PMID16538504 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Radiopharmaceuticals
  • Recombinant Fusion Proteins
  • Z(HER2.4)2 affibody
  • Receptor, ErbB-2
Topics
  • Animals
  • Cell Line, Tumor
  • Drug Delivery Systems (methods)
  • Female
  • Humans
  • Metabolic Clearance Rate
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Organ Specificity
  • Ovarian Neoplasms (metabolism, radionuclide imaging)
  • Radiopharmaceuticals (pharmacokinetics)
  • Receptor, ErbB-2 (metabolism)
  • Recombinant Fusion Proteins (pharmacokinetics)
  • Tissue Distribution

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: