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.

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

“…LET dosimetry of individual α-particle tracks was performed to assess the absorbed dose in tissues. Figure 2 shows the LET spectrum of observed α-particle tracks with a peak at around 130 keV/μm, as is consistent with previous work using 211 At-binding cells (19). The absorbed dose ( D ) was calculated using Equation 3 in locally segmented cells binned in a square size of 10 × 10 μm, which is comparable to the typical mean cell diameter of 10 μm (28).…”

“…Recently, we reported that the binding efficiency of 211 At-labeled antibodies to targeted cells had been verified by a one-to-one correspondence investigation (i.e., the number of α-particle traversals per individual cell) using CR-39 plastic nuclear track detectors (19). The CR-39 is a promising tool for microscopic dosimetry on a single-cell level based on LET spectroscopy with a submicron spatial resolution (20).…”

“…The CR-39 is a promising tool for microscopic dosimetry on a single-cell level based on LET spectroscopy with a submicron spatial resolution (20). The high-speed imaging capability of the microscope (21)—currently reaching 30 s/cm 2 —allows autoradiographic imaging of the spatial dose distribution in tissue at a microscopic resolution (19). Moreover, the CR-39 responds only to heavily charged particles (LET ≥ 3.5 keV/μm) without any contamination by photons (20).…”

Development of an ultrahigh-resolution, real-time alpha-particle imaging system for observing the trajectories of alpha particles in a scintillator

“…High-resolution alpha-particle imaging is required for the distribution measurements in cells or dissected animals for the development of new radio-compounds and dosimetry for targeted alpha-particle therapy [1][2][3]. High-resolution alpha-particle imaging is also required for distribution measurements in mineralogical studies [4] as well as plutonium (Pu) particle detection at nuclear facilities [5][6].…”

α‐particle therapy for synovial sarcoma in the mouse using an astatine‐211‐labeled antibody against frizzled homolog 10

“…Astatine‐211 ( 211 At) is one of the more attractive α‐emitters in this regard because of its 7.2‐h half‐life and 100% α‐particle emission during its decay . The remarkably high cell killing potency of 211 At derives from its high energy transfer within a short range of the α‐particle, which is considered to be stronger than that of a β‐particle . We have previously reported, also in a preclinical mouse model, that α‐RIT using 211 At‐labeled trastuzumab is highly effective against peritoneal metastases of gastric cancers that are positive for human epidermal growth factor receptor 2 (HER2) .…”