Production of 64Cu-labeled monobody for imaging of human EphA2-expressing tumors

Bioorg Med Chem Lett. 2020 Jul 15;30(14):127262. doi: 10.1016/j.bmcl.2020.127262. Epub 2020 May 15.

Abstract

We previously reported on the monobody E1, which specifically targets the tumor marker hEphA2. In this study, we labeled NOTA-conjugated E1 with 64Cu (64Cu-NOTA-E1) and evaluated biologic characteristics. The uptake of 64Cu-NOTA-E1 in PC3 cells (a human prostate cancer cell line) with high expression of hEphA2 increased in a time-dependent manner. In PC3 xenograft mice, 64Cu-NOTA-E1 injected via the tail vein allowed visualization of tumors on positron emission tomography after 1 h and the highest uptake measured at 24 h post-injection. By contrast, the radioactivity of other tissues either did not increase or decreased over 24 h. This indicates that 64Cu-NOTA-E1 has high tumor uptake and retention, with rapid clearance, and low background values in other tissues. Therefore, 64Cu-NOTA-E1 should be suitable as a novel PET imaging agent for hEphA2-expressing tumors.

Keywords: (64)Cu labeling; Human EphA2; Molecular imaging; Monobody; Positron emission tomography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / chemistry*
  • Copper Radioisotopes
  • Ephrin-A2 / chemistry
  • Ephrin-A2 / genetics*
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Humans
  • Male
  • Mice
  • Molecular Structure
  • Neoplasms, Experimental / diagnostic imaging
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / metabolism
  • PC-3 Cells
  • Positron-Emission Tomography*
  • Prostatic Neoplasms / diagnostic imaging*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Receptor, EphA2

Substances

  • Antibodies
  • Copper Radioisotopes
  • EPHA2 protein, human
  • Ephrin-A2
  • Heterocyclic Compounds, 1-Ring
  • 1,4,7-triazacyclononane-N,N',N''-triacetic acid
  • Receptor, EphA2