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

Abstract

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.

α-Emitters for Radiotherapy: From Basic Radiochemistry to Clinical Studies—Part 1

“…During 212 Pb decay, g-ray emissions compete with internal conversion over 30% of the time. The ejection of conversion electrons brings 212 Bi to highly ionized states (e.g., Bi 51 and Bi 71 ), destabilizing the bismuth complexes and ultimately liberating the radionuclide (32). Although free 212 Pb accumulates in the blood, liver, bone, and kidneys, 212 Bi accumulates mainly in the kidneys and urine.…”

“…This approach, developed by Arazi et al, involves local administration of wire sources impregnated with radionuclides such as 224 Ra in or near the solid tumor tissue (51). Necrotic regions of several millimeters were observed around the therapeutic source in several tumor models (Fig.…”

Ion and Neutron Beams Discover New Facts from History

“…A method that makes a virtue of the necessity to consider the diffusion of daughter isotopes to deliberately enhance the range of action in solid tumours has been proposed recently [Ara07]; it is termed diffusing alpha-emitters radiation therapy (DART) and it can be conceptually classified as a brachytherapy method. The basic idea is to treat tumours by intra-tumoral implantation of specially prepared radioactive sources of relatively low activity, which continually release short lived α-emitting atoms from their surface.…”

The Radiochemical and Radiopharmaceutical Applications of Radium

“…This method does have its drawbacks though. Due to its long half-life, 212 Pb was observed to migrate away from the tumor resulting in a higher dose to several organs, most notably the kidneys and liver [82]. The amount of radionuclide escaped was relative to the size of the tumor; 90% 212 Pb leakage in a 0.1 g tumor, but only 12% in a 2.4 g tumor.…”