Validating α-particle emission from 211At-labeled antibodies in single cells for cancer radioimmunotherapy using CR-39 plastic nuclear track detectors

PLoS One. 2017 Jun 28;12(6):e0178472. doi: 10.1371/journal.pone.0178472. eCollection 2017.

Abstract

Recently, 211At has received increasing attention as a potential radionuclide for cancer radioimmunotherapy. It is a α-particle emitter, which is extremely effective against malignant cells. We demonstrate a method to verify the efficiency of 211At-labeled trastuzumab antibodies (211At-trastuzumab) against HER2 antigens, which has not been determined for radioimmunotherapy. A CR-39 plastic nuclear detector is used for measuring the position and the linear energy transfer (LET) of individual 211At α- particle tracks. The tracks and 211At-trastuzumab-binding cells were co-visualized by using the geometric information recorded on the CR-39. HER2-positive human gastric cancer cells (NCI-N87), labelled with 211At-trastuzumab, were dropped on the centre of the CR-39 plate. Microscope images of the cells and the corresponding α-tracks acquired by position matching were obtained. In addition, 3.5 cm × 3.5 cm macroscopic images of the whole plate were acquired. The distribution of number of α-particles emitted from single cells suggests that 80% of the 211At-trastuzumab-binding cells emitted α-particles. It also indicates that the α-particles may strike the cells several times along their path. The track-averaged LET of the α-particles is evaluated to be 131 keV/μm. These results will enable quantitative evaluation of delivered doses to target cells, and will be useful for the in vitro assessment of 211At-based radioimmunotherapeutic agents.

Publication types

  • Validation Study

MeSH terms

  • Alpha Particles / therapeutic use*
  • Antibodies, Monoclonal / therapeutic use*
  • Astatine / chemistry*
  • Cell Line, Tumor
  • Humans
  • Plastics / chemistry*
  • Polyethylene Glycols / chemistry*
  • Radioimmunotherapy / methods*

Substances

  • Antibodies, Monoclonal
  • Plastics
  • CR 39
  • Polyethylene Glycols
  • Astatine

Grants and funding

This work was supported by the President's grant from National Institute of Radiological Sciences to SH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.