Comparative in vitro microdosimetric study of murine- and human-derived cancer cells exposed to alpha particles.

Diffusing alpha-emitter radiation therapy (DaRT) is a proposed new form of brachytherapy using α particles to treat solid tumors. The method relies on implantable ²²4Ra-loaded sources that continually release short-lived α-particle-emitting atoms that spread inside the tumor over a few millimeters. This treatment was demonstrated to have a significant effect on tumor growth in murine and human-derived models, but the degree of tumor response varied across cell lines. Tumor response was found to correlate with the degree of radionuclide spread inside the tumor. In this work we examined the radiosensitivity of individual cells to determine its relationship to tumor response. Cells were irradiated in vitro by α particles using a ²²8Th irradiator, with the mean lethal dose, D0, estimated from survival curves generated by standard methods. The results were further analyzed by microdosimetric tools to calculate z0, the specific energy resulting in a survival probability of 1/e for a single cell, which is considered to better represent the intrinsic radiosensitivity of individual cells. The results of the study demonstrate that, as a rule, tumors that respond more favorably to the DaRT treatment are also characterized by higher intrinsic cellular radiosensitivities, with D0 ranging from 0.7 Gy to 1.5 Gy for the extreme cases and z0 following the same trend.

The treatment of solid tumors by alpha emitters released from (224)Ra-loaded sources-internal dosimetry analysis.

Diffusing alpha-emitters radiation therapy (DART) is a proposed new form of brachytherapy, allowing the treatment of solid tumors by alpha particles. DART utilizes implantable sources carrying small activities of radium-224, which continually release into the tumor radon-220, polonium-216 and lead-212 atoms, while radium-224 itself remains fixed to the source. The released atoms disperse inside the tumor by diffusive and convective processes, creating, through their alpha emissions, a high-dose region measuring several mm in diameter about each source. The efficacy of DART has been demonstrated in preclinical studies on mice-borne squamous cell carcinoma and lung tumors and the method is now being developed toward clinical trials. This work studies DART safety with respect to the dose delivered to distant organs as a result of lead-212 leakage from the tumor through the blood, relying on a biokinetic calculation coupled to internal dose assessments. It is found that the dose-limiting organs are the kidneys and red bone marrow. Assuming a typical source spacing of approximately 5 mm and a typical radium-224 activity density of 0.4-0.8 MBq g(-1) of tumor tissue, it is predicted that tumors weighing up to several hundred grams may be treated without reaching the tolerance dose in any organ.

Treatment of solid tumors by interstitial release of recoiling short-lived alpha emitters.

A new method utilizing alpha particles to treat solid tumors is presented. Tumors are treated with interstitial radioactive sources which continually release short-lived alpha emitting atoms from their surface. The atoms disperse inside the tumor, delivering a high dose through their alpha decays. We implement this scheme using thin wire sources impregnated with (224)Ra, which release by recoil (220)Rn, (216)Po and (212)Pb atoms. This work aims to demonstrate the feasibility of our method by measuring the activity patterns of the released radionuclides in experimental tumors. Sources carrying (224)Ra activities in the range 10-130 kBq were used in experiments on murine squamous cell carcinoma tumors. These included gamma spectroscopy of the dissected tumors and major organs, Fuji-plate autoradiography of histological tumor sections and tissue damage detection by Hematoxylin-Eosin staining. The measurements focused on (212)Pb and (212)Bi. The (220)Rn/(216)Po distribution was treated theoretically using a simple diffusion model. A simplified scheme was used to convert measured (212)Pb activities to absorbed dose estimates. Both physical and histological measurements confirmed the formation of a 5-7 mm diameter necrotic region receiving a therapeutic alpha-particle dose around the source. The necrotic regions shape closely corresponded to the measured activity patterns. (212)Pb was found to leave the tumor through the blood at a rate which decreased with tumor mass. Our results suggest that the proposed method, termed DART (diffusing alpha-emitters radiation therapy), may potentially be useful for the treatment of human patients.