Design, synthesis and validation of integrin α2β1-targeted probe for microPET imaging of prostate cancer

  • Chiun-Wei Huang
  • Zibo Li
  • Hancheng Cai
  • Kai Chen
  • Tony Shahinian
  • Peter S Conti
Original Article

DOI: 10.1007/s00259-011-1752-x

Cite this article as:
Huang, CW., Li, Z., Cai, H. et al. Eur J Nucl Med Mol Imaging (2011) 38: 1313. doi:10.1007/s00259-011-1752-x

Abstract

Purpose

The ability of PET to aid in the diagnosis and management of recurrent and/or disseminated metastatic prostate cancer may be enhanced by the development of novel prognostic imaging probes. Accumulating experimental evidence indicates that overexpression of integrin α2β1 may correlate with progression in human prostate cancer. In this study, 64Cu-labeled integrin α2β1-targeted PET probes were designed and evaluated for the imaging of prostate cancer.

Methods

DGEA peptides conjugated with a bifunctional chelator (BFC) were developed to image integrin α2β1 expression with PET in a subcutaneous PC-3 xenograft model. The microPET images were reconstructed by a two-dimensional ordered subsets expectation maximum algorithm. The average radioactivity accumulation within a tumor or an organ was quantified from the multiple region of interest volumes.

Results

The PET tracer demonstrated prominent tumor uptake in the PC-3 xenograft (integrin α2β1-positive). The receptor specificity was confirmed in a blocking experiment. Moreover, the low tracer uptake in a CWR-22 tumor model (negative control) further confirmed the receptor specificity.

Conclusion

The sarcophagine-conjugated DGEA peptide allows noninvasive imaging of tumor-associated α2β1 expression, which may be a useful PET probe for evaluating the metastatic potential of prostate cancer.

Keywords

Integrin α2β1 Metastatic biomarker Prostate tumor imaging DGEA peptide microPET imaging 

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Chiun-Wei Huang
    • 1
  • Zibo Li
    • 1
  • Hancheng Cai
    • 1
  • Kai Chen
    • 1
  • Tony Shahinian
    • 1
  • Peter S Conti
    • 1
  1. 1.Department of RadiologyUniversity of Southern CaliforniaLos AngelesUSA