Development of an optimal imaging strategy for selection of patients for affibody-based PNA-mediated radionuclide therapy

Sci Rep. 2018 Jun 25;8(1):9643. doi: 10.1038/s41598-018-27886-0.

Abstract

Affibody molecules are engineered scaffold proteins, which demonstrated excellent binding to selected tumor-associated molecular abnormalities in vivo and highly sensitive and specific radionuclide imaging of Her2-expressing tumors in clinics. Recently, we have shown that peptide nucleic acid (PNA)-mediated affibody-based pretargeted radionuclide therapy using beta-emitting radionuclide 177Lu extended significantly survival of mice bearing human Her2-expressing tumor xenografts. In this study, we evaluated two approaches to use positron emission tomography (PET) for stratification of patients for affibody-based pretargeting therapy. The primary targeting probe ZHER2:342-SR-HP1 and the secondary probe HP2 (both conjugated with DOTA chelator) were labeled with the positron-emitting radionuclide 68Ga. Biodistribution of both probes was measured in BALB/C nu/nu mice bearing either SKOV-3 xenografts with high Her2 expression or DU-145 xenografts with low Her2 expression. 68Ga-HP2 was evaluated in the pretargeting setting. Tumor uptake of both probes was compared with the uptake of pretargeted 177Lu-HP2. The uptake of both 68Ga-ZHER2:342-SR-HP1 and 68Ga-HP2 depended on Her2-expression level providing clear discrimination of between tumors with high and low Her2 expression. Tumor uptake of 68Ga-HP2 correlated better with the uptake of 177Lu-HP2 than the uptake of 68Ga-ZHER2:342-SR-HP1. The use of 68Ga-HP2 as a theranostics counterpart would be preferable approach for clinical translation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic
  • Female
  • Isotope Labeling
  • Mice
  • Patient Selection*
  • Peptide Nucleic Acids / metabolism*
  • Positron Emission Tomography Computed Tomography / methods*
  • Radiotherapy*
  • Receptor, ErbB-2 / metabolism
  • Recombinant Fusion Proteins*

Substances

  • Peptide Nucleic Acids
  • Recombinant Fusion Proteins
  • affibody (ZHER2-342)2
  • ERBB2 protein, human
  • Receptor, ErbB-2