Production, isolation, and shipment of clinically relevant quantities of astatine-211: A simple and efficient approach to increasing supply.

The alpha emitter astatine-211 (211At) is a promising candidate for cancer treatment based on Targeted Alpha (α) Therapy (TAT). A small number of facilities, distributed across the United States, are capable of accelerating α-particle beams to produce 211At. However, challenges remain regarding strategic methods for shipping 211At in a form adaptable to advanced radiochemistry reactions and other uses of the radioisotope. PURPOSE: Our method allows shipment of 211At in various quantities in a form convenient for further radiochemistry. PROCEDURES: For this study, a 3-octanone impregnated Amberchrom CG300M resin bed in a column cartridge was used to separate 211At from the bismuth matrix on site at the production accelerator (Texas A&M) in preparation for shipping. Aliquots of 6 M HNO3 containing up to ≈2.22 GBq of 211At from the dissolved target were successfully loaded and retained on columns. Exempt packages (<370 MBq) were shipped to a destination radiochemistry facility, University of Texas MD Anderson Cancer Center, in the form of a convenient air-dried column. Type A packages have been shipped overnight to University of Alabama at Birmingham. MAIN FINDINGS: Air-dried column hold times of various lengths did not inhibit simple and efficient recovery of 211At. Solution eluted from the column was sufficiently high in specific activity to successfully radiolabel a model compound, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1), with 211At. The method to prepare and ship 211At described in this manuscript has also been used to ship larger quantities of 211At a greater distance to University of Alabama at Birmingham. PRINCIPAL CONCLUSIONS: The successful proof of this method paves the way for the distribution of 211At from Texas A&M University to research institutions and clinical oncology centers in Texas and elsewhere. Use of this simple method at other facilities has the potential increase the overall availability of 211At for preclinical and clinical studies.

Monte Carlo simulation study to explore optimum conditions for Astatine-211 SPECT.

211At is a promising nuclide for targeted radioisotope therapy. Direct imaging of this nuclide is important for in vivo evaluation of its distribution. We investigated suitable conditions for single-photon emission computed tomography (SPECT) imaging of 211At and assessed their feasibility using a homemade Monte Carlo simulation code, MCEP-SPECT. Radioactivity concentrations of 5, 10, or 20 kBq/mL were distributed in six spheres in a National Electrical Manufactures Association (NEMA) body phantom with a background of 1 kBq/mL. The energy window, projection number, and acquisition time were 71-88 keV, 60, and 60 s, respectively, per projection. A medium-energy collimator and three low-energy collimators were tested. SPECT images were reconstructed using the ordered subset expectation maximization (OSEM) method with attenuation correction (Chang method) and scatter correction (triple-energy-windows method). Image quality was evaluated using the contrast-to-noise ratio (CNR) for detectability and the contrast recovery coefficient (CRC) for quantitavity. The low-energy, high-sensitivity collimator exhibited the best detectability among the four types of collimators, with a maximum CNR value of 43. In contrast, the low-energy, high-resolution collimator exhibited excellent quantitavity, with a maximum CRC value of 102%. Scatter correction improved the image quality. In particular, the CRC value almost doubled after scatter correction. The detection of spheres smaller than 20 mm in diameter was difficult. In summary, low-energy collimators were suitable for the SPECT imaging of 211At. In addition, scatter correction was extremely effective in improving the image quality. The feasibility of 211At SPECT was demonstrated for lesions larger than 20 mm.

Targeted α-therapy using astatine (211At)-labeled PSMA1, 5, and 6: a preclinical evaluation as a novel compound.

PURPOSE: Targeted α-therapy (TAT) for prostate-specific membrane antigen (PSMA) is a promising treatment for metastatic castration-resistant prostate cancer (CRPC). Astatine is an α-emitter (half-life=7.2 h) that can be produced by a 30-MeV cyclotron. This study evaluated the treatment effect of 211At-labeled PSMA compounds in mouse xenograft models. METHODS: Tumor xenograft models were established by subcutaneous transplantation of human prostate cancer cells (LNCaP) in NOD/SCID mouse. [211At]PSMA1, [211At]PSMA5, or [211At]PSMA6 was administered to LNCaP xenograft mice to evaluate biodistribution at 3 and 24 h. The treatment effect was evaluated by administering [211At]PSMA1 (0.40 ± 0.07 MBq), [211At]PSMA5 (0.39 ± 0.03 MBq), or saline. Histopathological evaluation was performed for the at-risk organs at 3 and 6 weeks after administration. RESULTS: [211At]PSMA5 resulted in higher tumor retention compared to [211At]PSMA1 and [211At]PSMA6 (30.6 ± 17.8, 12.4 ± 4.8, and 19.1 ± 4.5 %ID/g at 3 h versus 40.7 ± 2.6, 8.7 ± 3.5, and 18.1 ± 2.2%ID/g at 24 h, respectively), whereas kidney excretion was superior in [211At]PSMA1 compared to [211At]PSMA5 and [211At]PSMA6. An excellent treatment effect on tumor growth was observed after [211At]PSMA5 administration. [211At]PSMA1 also showed a substantial treatment effect; however, the tumor size was relatively larger compared to that with [211At]PSMA5. In the histopathological evaluation, regenerated tubules were detected in the kidneys at 3 and 6 weeks after the administration of [211At]PSMA5. CONCLUSION: TAT using [211At]PSMA5 resulted in excellent tumor growth suppression with minimal side effects in the normal organs. [211At]PSMA5 should be considered a new possible TAT for metastatic CRPC, and translational prospective trials are warranted.

[Research and Development of 211At-MABG, 225Ac Production, and Anti-Podoplanin Antibody Therapy in Japan].

In Japan, research and development of"targeted radioisotope therapy: TRT"or"targeted α therapy: TAT"is focusing the 2 α nuclides, 225Ac, 211At. In this article, I would like to provide a brief summary of the following TAT agents, 211At-MABG and 225Ac anti-podoplanin antibody.

[Investigator-Initiated Clinical Trial of 211At-NaAt against Refractory Thyroid Cancer].

Radioactive iodine has long been used clinically for patients with differentiated thyroid cancer. Radioiodine(131I) is used for the ablation of thyroid remnants or treatment of metastatic thyroid cancer. However, some patients with multiple metastases are refractory to repetitive 131I treatment, despite the targeted regions showing sufficient iodine uptake. In such patients, ß- particle therapy using 131I is inadequate and another strategy is needed using more effective radionuclide targeting the sodium/iodide symporter(NIS). Astatine(211At)is receiving increasing attention as an α-emitter for targeted radionuclide therapy. 211At is a halogen element with similar chemical properties to iodine. α particles emitted from 211At has higher linear energy transfer as compared to ß particles from 131I and exert a better therapeutic effect by inducing DNA double strand breaks and free radical formation. We showed that increase of the radiochemical purity of astatide of 211At solution by addition of ascorbic acid was associated with significantly enhanced uptake of 211At by both normal thyroid tissue and differentiated thyroid cancer cells. The treatment effect of 211At solution in the K1-NIS xenograft model was dose-dependent and was associated with prolonged survival, suggesting the potential applicability of targeted α therapy for the treatment of advanced differentiated thyroid cancer. Thus, targeted α therapy using 211At is highly promising for the treatment of advanced differentiated thyroid cancer. We have already started the clinical trial of 211At-NaAt in Osaka University Hospital since November 2021 after getting the approval by IRB and PMDA investigation. We would like to get the proof of concept that astatine can be used safely and effectively in patients, aiming at the drug approval as a targeted α therapeutic from Japan.

Comparison of the Therapeutic Effects of [211At]NaAt and [131I]NaI in an NIS-Expressing Thyroid Cancer Mouse Model.

Astatine (211At) is an alpha-emitter with a better treatment efficacy against differentiated thyroid cancer compared with iodine (131I), a conventional beta-emitter. However, its therapeutic comparison has not been fully evaluated. In this study, we compared the therapeutic effect between [211At]NaAt and [131I]NaI. In vitro analysis of a double-stranded DNA break (DSB) and colony formation assay were performed using K1-NIS cells. The therapeutic effect was compared using K1-NIS xenograft mice administered with [211At]NaAt (0.4 MBq (n = 7), 0.8 MBq (n = 9), and 1.2 MBq (n = 4)), and [131I]NaI (1 MBq (n = 4), 3 MBq (n = 4), and 8 MBq (n = 4)). The [211At]NaAt induced higher numbers of DSBs and had a more reduced colony formation than [131I]NaI. In K1-NIS mice, dose-dependent therapeutic effects were observed in both [211At]NaAt and [131I]NaI. In [211At]NaAt, a stronger tumour-growth suppression was observed, while tumour regrowth was not observed until 18, 25, and 46 days after injection of 0.4, 0.8, and 1.2 MBq of [211At]NaAt, respectively. While in [131I]NaI, this was observed within 12 days after injection (1, 3, and 8 MBq). The superior therapeutic effect of [211At]NaAt suggests the promising clinical applicability of targeted alpha therapy using [211At]NaAt in patients with differentiated thyroid cancer refractory to standard [131I]NaI treatment.

Complexation of Astatine(III) with Ketones: Roles of NO3- Counterion and Exploration of Possible Binding Modes.

Ketones have been proven effective in extracting astatine(III) from aqueous solvents. Previous theoretical studies suggested a mechanism where the "sp2" lone pair on the carbonyl oxygen donates electron density into the π system of the AtO+ molecular cation to form a dative-type bond. In this study, co-extraction of NO3- as AtO(NO3)·(O═CR1R2) species into the organic phase appears to be a key factor. Adjusting the electronic properties of the ketone, by having an aryl group instead of an alkyl group in the alpha position of the ketone, increased the electron density on C═O, increased the bond strength between the ketone and AtO+, and in turn increased the extraction of 211At into the organic phase. Extraction with diketones shows dependence on the bridging distance between the two carbonyl moieties, where a C3 or longer bridge results in a 10-fold increase in extraction into the organic phase. DFT calculations show the longer bridge allows for the chelation of AtO(NO3) by either the second carbonyl or the phenyl ring.

Preclinical Development of [211At]meta- astatobenzylguanidine ([211At]MABG) as an Alpha Particle Radiopharmaceutical Therapy for Neuroblastoma.

PURPOSE: [131I]meta-iodobenzylguanidine ([131I]MIBG) is a targeted radiotherapeutic administered systemically to deliver beta particle radiation in neuroblastoma. However, relapses in the bone marrow are common. [211At]meta-astatobenzylguanidine ([211At] MABG) is an alpha particle emitter with higher biological effectiveness and short path length which effectively sterilizes microscopic residual disease. Here we investigated the safety and antitumor activity [211At]MABG in preclinical models of neuroblastoma. EXPERIMENTAL DESIGN: We defined the maximum tolerated dose (MTD), biodistribution, and toxicity of [211At]MABG in immunodeficient mice in comparison with [131I]MIBG. We compared the antitumor efficacy of [211At]MABG with [131I]MIBG in three murine xenograft models. Finally, we explored the efficacy of [211At]MABG after tail vein xenografting designed to model disseminated neuroblastoma. RESULTS: The MTD of [211At]MABG was 66.7 MBq/kg (1.8 mCi/kg) in CB17SC scid-/- mice and 51.8 MBq/kg (1.4 mCi/kg) in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice. Biodistribution of [211At]MABG was similar to [131I]MIBG. Long-term toxicity studies on mice administered with doses up to 41.5 MBq/kg (1.12 mCi/kg) showed the radiotherapeutic to be well tolerated. Both 66.7 MBq/kg (1.8 mCi/kg) single dose and fractionated dosing 16.6 MBq/kg/fraction (0.45 mCi/kg) × 4 over 11 days induced marked tumor regression in two of the three models studied. Survival was significantly prolonged for mice treated with 12.9 MBq/kg/fraction (0.35 mCi/kg) × 4 doses over 11 days [211At]MABG in the disseminated disease (IMR-05NET/GFP/LUC) model (P = 0.003) suggesting eradication of microscopic disease. CONCLUSIONS: [211At]MABG has significant survival advantage in disseminated models of neuroblastoma. An alpha particle emitting radiopharmaceutical may be effective against microscopic disseminated disease, warranting clinical development.

Development of [211At]astatine-based anti-CD123 radioimmunotherapy for acute leukemias and other CD123+ malignancies.

Radioimmunotherapy (RIT) has long been pursued to improve outcomes in acute leukemia and higher-risk myelodysplastic syndrome (MDS). Of increasing interest are alpha-particle-emitting radionuclides such as astatine-211 (211At) as they deliver large amounts of radiation over just a few cell diameters, enabling efficient and selective target cell kill. Here, we developed 211At-based RIT targeting CD123, an antigen widely displayed on acute leukemia and MDS cells including underlying neoplastic stem cells. We generated and characterized new murine monoclonal antibodies (mAbs) specific for human CD123 and selected four, all of which were internalized by CD123+ target cells, for further characterization. All mAbs could be conjugated to a boron cage, isothiocyanatophenethyl-ureido-closo-decaborate(2-) (B10), and labeled with 211At. CD123+ cell targeting studies in immunodeficient mice demonstrated specific uptake of 211At-labeled anti-CD123 mAbs in human CD123+ MOLM-13 cell tumors in the flank. In mice injected intravenously with MOLM-13 cells or a CD123NULL MOLM-13 subline, a single dose of up to 40 µCi of 211At delivered via anti-CD123 mAb decreased tumor burdens and substantially prolonged survival dose dependently in mice bearing CD123+ but not CD123- leukemia xenografts, demonstrating potent and target-specific in vivo anti-leukemia efficacy. These data support the further development of 211At-CD123 RIT toward clinical application.

Basis for the ICRP's updated biokinetic model for systemic astatine.

The International Commission on Radiological Protection (ICRP) recently updated its biokinetic models for workers in a series of reports called the OIR (occupational intakes of radionuclides) series. A new biokinetic model for astatine (At), the heaviest member of the halogen family, was adopted in OIR Part 5 (ICRP in press). Occupational intakes of radionuclides: Part 5). This paper provides an overview of available biokinetic data for At; describes the basis for the ICRP's updated model for At; and tabulates dose coefficients for intravenous injection of each of the two longest lived and most important At isotopes,211At and210At. At-211 (T1/2= 7.214 h) is a promising radionuclide for use in targetedα-particle therapy due to several favourable properties including its half-life and the absence of progeny that could deliver significant radiation doses outside the region ofα-particle therapy. At-210 (T1/2= 8.1 h) is an impurity generated in the production of211At in a cyclotron and represents a potential radiation hazard via its long-lived progeny210Po (T1/2= 138 days). Tissue dose coefficients for injected210At and211At based on the updated model are shown to differ considerably from values based on the ICRP's previous model for At, particularly for the thyroid, stomach wall, salivary glands, lungs, spleen, and kidneys.

211 At and 125 I-Labeling of (Hetero)Aryliodonium Ylides: Astatine Wins Again.

Despite the growing interest in radioiodine and 211 At-labeled radiopharmaceuticals, the search for radiolabeling reactions has been somewhat neglected, resulting in a limited number of available radiosynthetic strategies. Herein we report a comparative study of nucleophilic 125 I and 211 At-labeling of aryliodonium ylides. Whereas radioiodination efficiency was low, 211 At-labeling performed efficiently on a broad scope of precursors. The most activated aryliodonium ylides led rapidly to quantitative reactions at room temperature in acetonitrile. For deactivated precursors, heating up to 90 °C in glyme and addition of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) as radical scavenger appeared essential to avoid precursor degradation and to achieve high radiochemical yields and molar activity. The approach was applied successfully to the preparation of 4-[211 At]astatophenylalanine (4-APA), an amino acid derivative increasingly studied as radiotherapeutic drug for cancers. This validated aryliodonium ylides as a valuable tool for nucleophilic 211 At-labeling and will complement the short but now growing list of available astatination reactions.

Neopentyl Glycol as a Scaffold to Provide Radiohalogenated Theranostic Pairs of High In Vivo Stability.

The high in vivo stability of 2,2-dihydroxymethyl-3-[18F]fluoropropyl-2-nitroimidazole ([18F]DiFA) prompted us to evaluate neopentyl as a scaffold to prepare a radiotheranostic system with radioiodine and astatine. Three DiFA analogues with one, two, or without a hydroxyl group were synthesized. While all 125I-labeled compounds remained stable against nucleophilic substitution, only a 125I-labeled neopentyl glycol was stable against cytochrome P450 (CYP)-mediated metabolism and showed high stability against in vivo deiodination. 211At-labeled neopentyl glycol also remained stable against both nucleophilic substitution and CYP-mediated metabolism. 211At-labeled neopentyl glycol showed the biodistribution profiles similar to those of its radioiodinated counterpart in contrast to the 125I/211At-labeled benzoate pair. The urine analyses confirmed that 211At-labeled neopentyl glycol was excreted in the urine as a glucuronide conjugate with the absence of free [211At]At-. These findings indicate that neopentyl glycol would constitute a promising scaffold to prepare a radiotheranostic system with radioiodine and 211At.

Synthesis and Preliminary Evaluation of 131I-Labeled FAPI Tracers for Cancer Theranostics.

As an excellent target for cancer theranostics, fibroblast activation protein (FAP) has become an attractive focus in cancer research. A class of FAP inhibitors (FAPIs) with a N-(4-quinolinoyl)-Gly-(2-cyanopyrrolidine) scaffold were developed, which displayed nanomolar affinity and high selectivity. Compared with 90Y, 177Lu, 225Ac, and 188Re, 211At seems to be more favored as a therapeutic candidate for FAPI tracers which have fast washout and short retention in tumor sites. Thus, the current study reported the synthesis of two FAPI precursors for 211At and 131I labeling and the preliminary evaluation of 131I-labeled FAPI analogues for cancer theranostics. FAPI variants with stannyl precursors were successfully synthesized and labeled with 131I using a radioiododestannylation reaction. Two radioactive tracers were obtained with high radiochemical purity over 99% and good radiochemical yields of 58.2 ± 1.78 and 59.5 ± 4.44% for 131I-FAPI-02 and 131I-FAPI-04, respectively. Both tracers showed high specific binding to U87MG cells in comparison with little binding to MCF-7 cells. Compared to 131I-FAPI-02, 131I-FAPI-04 exhibited higher affinity, more intracellular uptake, and longer retention time in vitro. Biodistribution studies revealed that both tracers were mainly excreted through the kidneys as well as the hepatobiliary pathway due to their high lipophilicity. In addition, higher accumulation, longer dwell time, and increased tumor-to-organ ratios were achieved by 131I-FAPI-04, which was clearly demonstrated by SPECT/CT imaging. Furthermore, intratumor injection of 131I-FAPI-04 significantly suppressed the tumor growth in U87MG xenograft mice without significant toxicity observed. The above results implied that FAP-targeted alpha endoradiotherapy (specific to 211At) should be used to treat tumors in the near future, considering the chemical similarity between iodine and astatine can ensure the labeling of the latter onto the designed FAPIs.

68Ga- and 211At-Labeled RGD Peptides for Radiotheranostics with Multiradionuclides.

Probes for radiotheranostics could be produced by introducing radionuclides with similar chemical characteristics into the same precursors. We recently developed an 211At-labeled RGD peptide and a corresponding radioiodine-labeled RGD peptide. Both labeled peptides accumulated in large quantities in the tumor with similar biodistribution, demonstrating their usefulness for radiotheranostics. In this study, we hypothesized that probes for radiotheranostics combined with multiradionuclides, such as 68Ga and 211At, have useful clinical applications. New radiolabeled RGD peptide probes were synthesized via a molecular design approach, with two labeling sites for metal and halogen. These probes were evaluated in biodistribution experiments using tumor-bearing mice. [67Ga]Ga-DOTA-c[RGDf(4-I)K] ([67Ga]4), Ga-DOTA-[125I]c[RGDf(4-I)K] ([125I]4), and Ga-DOTA-[211At]c[RGDf(4-At)K] ([211At]7) showed similar biodistribution, with high and equivalent accumulation in tumors. These results indicate the usefulness of these probes in radiotheranostics with multiradionuclides, such as a radiometal and a radiohalogen, and they could contribute to a personalized medicine regimen.

The sodium iodide symporter (NIS): novel applications for radionuclide imaging and treatment.

Cloning of the sodium iodide symporter (NIS) 25 years ago has opened an exciting chapter in molecular thyroidology with the characterization of NIS as one of the most powerful theranostic genes and the development of a promising gene therapy strategy based on image-guided selective NIS gene transfer in non-thyroidal tumors followed by application of 131I or alternative radionuclides, such as 188Re and 211At. Over the past two decades, significant progress has been made in the development of the NIS gene therapy concept, from local NIS gene delivery towards promising new applications in disseminated disease, in particular through the use of oncolytic viruses, non-viral polyplexes, and genetically engineered MSCs as highly effective, highly selective and flexible gene delivery vehicles. In addition to allowing the robust therapeutic application of radioiodine in non-thyroid cancer settings, these studies have also been able to take advantage of NIS as a sensitive reporter gene that allows temporal and spatial monitoring of vector biodistribution, replication, and elimination - critically important issues for preclinical development and clinical translation.

211At-Labeled Polymer Nanoparticles for Targeted Radionuclide Therapy of Glucose-Dependent Insulinotropic Polypeptide Receptor (GIPR)-Overexpressed Cancer.

Targeted radionuclide therapy (TRT) provides new and safe opportunities for cancer treatment and management with high precision and efficiency. Here we have designed a novel semiconducting polymer nanoparticle (SPN)-based radiopharmaceutical (211At-MeATE-SPN-GIP) for TRT against glucose-dependent insulinotropic polypeptide receptor (GIPR)-positive cancers to further explore the applications of nanoengineered TRT. 211At-MeATE-SPN-GIP was engineered via nanoprecipitation, followed by its functionalization with a glucose-dependent insulinotropic polypeptide (GIP) to target GIPR and deliver 211At for α therapy. The therapeutic effect and biological safety of 211At-MeATE-SPN-GIP were investigated using GIPR-overexpressing human pancreatic cancer CFPAC-1 cells and CFPAC-1-bearing mice. In this work, 211At-MeATE-SPN-GIP was produced with a radiochemical yield of 43% and radiochemical purity of 98%, which exhibited a specifically high uptake in CFPAC-1 cells, inducing cell cycle arrest at the G2/M phase and extensive DNA damage. In the CFPAC-1-bearing tumor model, 211At-MeATE-SPN-GIP exhibited high therapeutic efficiency, with no obvious side effects. The GIPR-specific binding of 211At-MeATE-SPN-GIP combined with effective inhibition of tumor growth and fewer side effects compared to control suggests that 211At-MeATE-SPN-GIP TRT holds great potential as a novel nanoengineered TRT strategy for patients with GIPR-positive cancer.

Intratumoral administration of astatine-211-labeled gold nanoparticle for alpha therapy.

BACKGROUND: 211At is a high-energy α-ray emitter with a relatively short half-life and a high cytotoxicity for cancer cells. Its dispersion can be imaged using clinical scanners, and it can be produced in cyclotrons without the use of nuclear fuel material. This study investigated the biodistribution and the antitumor effect of 211At-labeled gold nanoparticles (211At-AuNP) administered intratumorally. RESULTS: AuNP with a diameter of 5, 13, 30, or 120 nm that had been modified with poly (ethylene glycol) methyl ether (mPEG) thiol and labeled with 211At (211At-AuNP-S-mPEG) were incubated with tumor cells, or intratumorally administered to C6 glioma or PANC-1 pancreatic cancers subcutaneously transplanted into rodent models. Systemic and intratumoral distributions of the particles in the rodents were then evaluated using scintigraphy and autoradiography, and the changes in tumor volumes were followed for about 40 days. 211At-AuNP-S-mPEG was cytotoxic when it was internalized by the tumor cells. After intratumoral administration, 211At-AuNP-S-mPEG became localized in the tumor and did not spread to systemic organs during a time period equivalent to 6 half-lives of 211At. Tumor growth was strongly suppressed for both C6 and PANC-1 by 211At-AuNP-S-mPEG. In the C6 glioma model, the strongest antitumor effect was observed in the group treated with 211At-AuNP-S-mPEG with a diameter of 5 nm. CONCLUSIONS: The intratumoral single administration of a simple nanoparticle, 211At-AuNP-S-mPEG, was shown to suppress the growth of tumor tissue strongly in a particle size-dependent manner without radiation exposure to other organs caused by systemic spread of the radionuclide.

Simulation of the distribution of astatine-211 solution dispersion in a lab room.

OBJECTIVE: This study aimed to evaluate the distribution of Astatine-211 (211At) solution dispersion in a small animal cage using autoradiography imaging to simulate the dispersion of 211At in a lab room to eventually prevent user's risk of internal exposure in terms of radiation safety. METHODS: 211At radiation sources with two chemical properties (Na211At and Free 211At) were prepared. The solutions of 211At were placed onto a dish with paper, and then, it was placed in a small animal cage for 3 h. After removing the dish, an imaging plate with attaching reference sources was placed at four walls of the cage for 15 h in a lead box. Imaging plates were read, and all pixel data were calculated using Microsoft Excel 2016 to obtain three-dimensional (3D) distribution. Calculated results were depicted using a 3D sphere model. RESULTS: The mean activity of Free 211At was 2.3 times higher than that of Na211At on all autoradiography images. In the cage, the shape of the dispersion of Na211At was almost homogeneous, whereas that of Free 211At was more heterogeneous. CONCLUSION: We found that the solution of 211At vaporized naturally and was distributed heterogeneously in the cage, and the chemical properties of 211At influenced their behaviors. These results must be considered to minimize the risks of radiation safety.