Evidence of Local Concentration of α-Particles from 211At-Labeled Antibodies in Liver Metastasis Tissue.

Satoshi Kodaira,Huizi Keiko Li,Yukie Morokoshi,Sumitaka Hasegawa,Teruaki Konishi,Mieko Kurano

doi:10.2967/jnumed.118.216853

Abstract

We investigated the local concentration of α-particles from 211At-labeled trastuzumab antibodies against human epidermal growth factor receptor type 2 antigens in liver metastasis tissue of mice. Methods: Mice carrying metastatic cancer in their liver were injected with 211At-agent. After 12 h, the liver was removed and sliced, and 2 tissue samples of liver tissues without lesions and one containing metastatic lesions were mounted on the CR-39 plastic nuclear track detector. Microscope images of the tissues on the CR-39 were acquired. After irradiation for 31 h, the tissues were removed from the CR-39. A microscope image of α-particle tracks on the CR-39 was acquired after chemical etching. The positions of each tissue sample and the emitted α-particle tracks were adjusted to the same coordinates. Results: The positional distribution of α-particle tracks emitted from 211At was consistent within the tissue. The α-particle tracks were mainly allocated in the tumor region of the tissue. The absorbed dose in individual cells segmented by 10-μm intervals was obtained by the spectroscopic analysis of the linear-energy-transfer spectrum. The concentration efficiency—the track density ratio of α-particle tracks in the necrotized tissue, which was the tumor region, to the normal tissue—was found to be 6.0 ± 0.2. In the tumor region, the high–linear-energy-transfer α-particles deposited a large enough dose to cause lethal damage to the cancer cells. Conclusion: The total absorbed dose ranged from 1 to 7 Gy with a peak at around 2 Gy, which would correspond to a 2–3 times higher biologically equivalent dose because of the high relative biological effectiveness of the α-particles emitted from 211At.

Highlights

Radioimmunotherapy is more efficient with a-particle emitters than with conventional b-ray emitters because the former provides a high linear-energy transfer (LET) that can induce enough damage to break double-stranded DNA, as well as having a short range in tissue in order to target cancer cells but not the surrounding normal cells [1]
We reported that the binding efficiency of 211Atlabeled antibodies to targeted cells had been verified by a oneto-one correspondence investigation using CR-39 plastic nuclear track detectors [19]
Along the tissues reconstructed from the tiled microscope images (Fig. 1A), we could observe the a-particle tracks emitted from 211At distributed in the tissues in the scatterplot of the positions of the individual tracks (Fig. 1B)

Summary

Introduction

Radioimmunotherapy is more efficient with a-particle emitters than with conventional b-ray emitters because the former provides a high linear-energy transfer (LET) that can induce enough damage to break double-stranded DNA, as well as having a short range in tissue in order to target cancer cells but not the surrounding normal cells [1]. An aluminum oxide crystal–based device that detects a nuclear track by imaging a fluorescent track signal with a confocal microscope has been developed for radiation dosimetry [13,14,15] and single-cell radiobiology applications [16,17,18]. The DOSE DISTRIBUTION IN METASTASIS TISSUE Kodaira et al 497 available imaging area is strongly limited by the current low scan speed, which is on the order of several days for 1 cm. The DOSE DISTRIBUTION IN METASTASIS TISSUE Kodaira et al 497 available imaging area is strongly limited by the current low scan speed, which is on the order of several days for 1 cm2 This detector is not applicable to autoradiographic studies of animal samples that are on a scale of centimeters. The CR-39 responds only to heavily charged particles (LET $ 3.5 keV/mm) without any contamination by photons [20]

Results

Discussion

Conclusion