64Cu-Labeled Affibody Molecules for Imaging of HER2 Expressing Tumors View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-06

AUTHORS

Zhen Cheng, Omayra Padilla De Jesus, Daniel J. Kramer, Abhijit De, Jack M. Webster, Olivier Gheysens, Jelena Levi, Mohammad Namavari, Sen Wang, Jinha Mark Park, Rong Zhang, Hongguang Liu, Brian Lee, Faisal A. Syud, Sanjiv Sam Gambhir

ABSTRACT

INTRODUCTION: The development of molecular probes based on novel engineered protein constructs is under active investigation due to the great potential of this generalizable strategy for imaging a variety of tumor targets. DISCUSSION: In this report, human epidermal growth factor receptor type 2 (HER2)-binding Affibody molecules were radiolabeled with (64)Cu and their imaging ability was further evaluated in tumor mice models to understand the promise and limitations of such probes. The anti-HER2 Affibody molecules in monomeric (Z(HER2:477)) and dimeric [(Z(HER2:477))(2)] forms were site specifically modified with the maleimide-functionalized chelator, 1,4,7,10-tetraazacyclododecane-1,4,7-tris(acetic acid)-10-acetate mono (N-ethylmaleimide amide) (Mal-DOTA). The resulting DOTA-Affibody conjugates were radiolabeled with (64)Cu and evaluated in nude mice bearing subcutaneous SKOV3 tumors. Biodistribution experiments showed that tumor uptake values of (64)Cu-DOTA-Z(HER2:477) and (64)Cu-DOTA-(Z(HER2:477))(2) were 6.12 +/- 1.44% and 1.46 +/- 0.50% ID/g, respectively, in nude mice (n = 3 each) at 4 h postinjection. Moreover, (64)Cu-labeled monomer exhibited significantly higher tumor/blood ratio than that of radiolabeled dimeric counterpart at all time points examined in this study. MicroPET imaging of (64)Cu-DOTA-Z(HER2:477) in SKOV3 tumor mice clearly showed good and specific tumor localization. This study demonstrates that (64)Cu-labeled Z(HER2:477) is a promising targeted molecular probe for imaging HER2 receptor expression in living mice. Further work is needed to improve the excretion properties, hence dosimetry and imaging efficacy, of the radiometal-based probe. More... »

PAGES

316-324

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s11307-009-0256-6

DOI

http://dx.doi.org/10.1007/s11307-009-0256-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1000701038

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19779897


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