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

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.

Keywords: 211At radionuclide; autoradiography; dose distribution; microscopy; radioimmunotherapy; α-particle.

FIGURE 1.

(A) Photomicrograph of sliced tissues; left tissue has specifically localized tumors. (B) Scatterplot of detected α-particle tracks on CR-39. (C) Superposition of tissue image and scatterplot of α-particle tracks. (D) Contour map of α-particle track density in binned positions (Δx, Δy) with 50-μm intervals.

FIGURE 2.

LET spectrum of observed α-particles.

FIGURE 3.

Histogram of observed local absorbed dose for t = 12–43 h, estimated dose corrected by half-life of ²¹¹At decay for t = 0–12 h, and estimated total dose for t = 0–43 h. Doses are given in cell scale size (10 μm).

FIGURE 4.

Contour map of total local absorbed dose in binned positions (Δx, Δy) with 10-μm intervals.