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 211 At-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 211 At-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 211 At 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 211 At.

Utility of 211At-Trastuzumab for the Treatment of Metastatic Gastric Cancer in the Liver: Evaluation of a Preclinical α-Radioimmunotherapy Approach in a Clinically Relevant Mouse Model

“…Hence, an effective and accurate dose estimation in the normal liver and metastatic tumors is of particular importance. We have here estimated the appropriate radiation dose for the normal liver and metastatic tumors using two different approaches; a biodistribution-based dose estimation and microdosimetry using a CR-39 plastic detector that we have previously reported (21). The tumor to liver ratios in in absorbed dose at 24 hours after injection were 1.6 and 11.5 in the biodistribution-based dose estimation and the microdosimetry, respectively (Table 1 and Figure 5B).…”

Narrative review of the role of yttrium-90 selective internal radiation therapy in the surgical management of colorectal liver metastases

“…The concern about the low energy transfer and resistance development of betaemitting radioisotope has led many investigators to look for alternatives (63). Targeted alpha-particle therapy (TAT) has been emerging as a potential treatment for metastatic disease using alpha-emitting particles such as Actinium-225 ( 225 Ac), astatine-211 ( 211 At), and Lead-212 ( 212 Pb) (64,65). They provide a short range of high linear energy transfer to cancer cells with minimal toxicity to surrounding tissues.…”

Evaluation of CR-39 Track Parameters by Utilizing Chemical Organic Additives to NaOH Etchant

“…Subsequently, the area of the broken molecular chain (scission) is dissolved, and the resulting hole can become enlarged by factors of 10 2 to 10 3 . Solid-state nuclear track detectors (SSNTDs) have been successfully employed in different applications in science and technology [1], including in alpha autoradiography [2], radiation dosimetry [3] and particle identification [4].…”

“…Figure (2) shows the relation between the track densities at different etching time where the maximum track density is obtained around 6 hours etching times. The track diameter is increasing with etching time as shown in Figure (3) where the relationship is close to the linear form.…”