|
内容記述 |
Alpha emitters offer the potential to deliver high linear energy transfer (LET) radiation directly to tumors, primarily due to their short path length in biological tissues (<100 μm in water). This property has garnered increasing interest in its application for targeted radionuclide therapy[1], which is currently under active investigation in clinical trials. Among these, astatine-211 (211At) stands out due to its favorable radiophysical characteristics[2]. It emits a single alpha particle per decay with 100% alpha emission, minimizing the risk of unpredictable dose distribution that can result from the release of radioactive daughter nuclides—a common issue with other alpha emitters such as thorium-227, radium-223, lead-212, bismuth-212, and actinium-225, which undergo complex decay chains and may suffer from recoil-induced daughter release. In addition to its decay simplicity, 211At possesses a half-life (t₁/₂) of 7.2 hours, which offers a practical balance between physical decay and logistical considerations. Less than 1% of its radioactivity remains after 48 hours, potentially reducing off-target radiation exposure to normal tissues. Simultaneously, the half-life is sufficient to allow for transportation (up to approximately 3 hours) and subsequent radiolabeling procedures, with adequate activity remaining for clinical application. Due to its high LET, 211At is expected to exhibit potent cytotoxicity within targeted cells. Accurate estimation of the absorbed radiation dose in the targeted area is therefore essential for evaluating the therapeutic efficacy of 211At-labeled antibodies. Moreover, the overall effectiveness of treatment is influenced by the binding affinity and biological distribution of the targeting antibody, which determines the amount of radioactivity delivered to the tumor site. Because multiple alpha particle traversals are generally required to induce cell death, the number of effective "hits" per cell—and their corresponding energy deposition—varies depending on both the specific cell type and the physical characteristics of the emitted particles[3]. Thus, quantifying both the spatial energy deposition and the number of cellular hits is critical for assessing the safety, pharmacokinetics, and therapeutic potential of targeted alpha particle therapy using 211At. Aluminum oxide doped with carbon and magnesium (Al2O3:C,Mg)- based fluorescent nuclear track detector (FNTD) is a highly promising dosimeter for this application. It offers superior particle identification capabilities, along with high energy and spatial resolutions, and enables in situ measurement under a fluorescent microscope. It has the ability to measure and distinguish individual alpha tracks with high density, yielding a rich amount of information regarding the planar distribution, incident angle, alpha energy, and LET of individual particles[4]. In this study, we employed the FNTDs to record the 3D trajectories of alpha particle emission and estimate the residual energy deposition within single cells. |
