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

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.

Fig 1. Schematic of the experimental procedure.

Fig 2. Microscope images of cells and emitted α-tracks from those cells on aCR-39 detector.

A) Cells and B) corresponding α-tracks. A dot arrow indicates that no α-tracks are observed in the corresponding cell position. The enlarged images of C) cells and D) α-tracks recognized by ellipse fitting result are inset by the colored circles.

Fig 3. Scatter plots and contour maps of cells and α-tracks positions.

Scatter plots of the positions of A) cells and B) α-tracks over the entire surface of the CR-39 detector and C) their overlay, respectively. The macroscopic autoradiography as a contour map by counting the number of D) cells and E) α-tracks in binned positions (Δx, Δy) with 200 μm intervals.

Fig 4. The number of cells N_cell vs. α-tracks (N_α) and α-particles (Nα¯).

A) The observed number of α-tracks (N_α) emitted from single cells and B) the estimated number of α-particles ($\overline{N_{\mathrm{\alpha }}}$) corrected with solid angular and critical angular dependencies.

Fig 5. LET spectrum of α-particles from single cells.