Controlled release of radionuclides
Inventors
Kelson, Itzhak • Keisari, Yona • Schmidt, Michael • Gat, Amnon • Magen, Ofer • Keret, Guy • Sosnovitch, Amitai • Berkowitz, Avia
Assignees
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Publication Number
US-11969485-B2
Publication Date
2024-04-30
Expiration Date
Abstract
A brachytherapy device including a base adapted for being at least partially introduced into a body of a subject and a plurality of radionuclide atoms of a first alpha-emitting isotope, coupled to the base in a manner that not more than 15% of the radionuclide atoms leave the base in 24 hours, in methods other than radioactive decay. When installed in a human subject, the brachytherapy device emits radionuclide atoms of the first alpha-emitting isotope at a rate of at least 0.1% of the number of radionuclide atoms of the first alpha-emitting isotope coupled to the base, per 24 hours.
Core Innovation
The invention concerns a brachytherapy device that enables controlled desorb/diffuse release of a fraction of alpha-emitting parent radionuclide atoms from a seed base while limiting escape of radiation into healthy tissue. A plurality of radionuclide atoms of a first alpha-emitting isotope is coupled to the seed base so that at least 0.1%, but not more than 25% of the plurality leaves the seed base in 24 hours without radioactive decay, and daughter nuclei of the plurality are released from the seed base upon radioactive decay.
To control the release behavior, the invention includes coating structures and engineered release performance. In one aspect, radionuclide atoms diffuse from the seed base through a semi-porous polymer coating layer, and the coating can be dimensioned or material-selected, including polycarbonate and PDMS, to configure diffusion of at least 0.1% of particles of Radium-224 or Radium-223. In another aspect, multi-layer coatings include a first coating layer that prevents passage of Radium-224 or Radium-223 and a second coating layer that allows diffusion of the radionuclide particles.
The invention also provides probe-based brachytherapy devices that retain parent radionuclides in the probe while therapeutic emissions from decay chain radionuclides and alpha particles leave the probe surface. Particles of Radium-224 are retainably embedded on or beneath a surface of a probe so that the particles remain in the probe while decay chain radionuclides and alpha particles of the Radium-224 leave the surface. Particles of Thorium-228 are retainably embedded on or beneath the surface in a manner ensuring retention of Thorium-228 while decay chain radionuclides and alpha particles leave the surface, with an activity level of Thorium-228 lower than 50% of the activity level of Radium-224 in the device.
Claims Coverage
The document provides three independent claim families covering controlled parent radionuclide leave-from-seed behavior and daughter release on decay, a coated seed-base with a first layer preventing passage and a second layer enabling diffusion, and a probe device with retainably embedded Radium-224 and Thorium-228 and an activity-level relationship.
Controlled leave of parent radionuclide atoms with daughter release on decay
A brachytherapy device including a seed base adapted for being at least partially introduced into a body of a subject, with a plurality of radionuclide atoms of a first alpha-emitting isotope coupled to the seed base such that at least 0.1%, but not more than 25% of the plurality of radionuclide atoms leave the seed base in 24 hours, without radioactive decay, wherein daughter nuclei of the plurality of radionuclide atoms are released from the seed base upon radioactive decay.
First coating layer preventing passage and second coating layer enabling diffusion
A brachytherapy device including a seed base adapted for being at least partially introduced into a body of a subject, a first coating layer on the seed base configured to prevent passage of Radium-224 or Radium-223 therethrough, particles of a Radium-224 or Radium-223 radionuclide placed on the first coating layer, and a second coating layer on the particles configured to allow diffusion of at least 0.1% of the particles of the Radium-224 or Radium-223.
Retainably embedded Radium-224 and Thorium-228 with activity-level relationship
A brachytherapy device including a probe adapted for being at least partially introduced into a body of a subject, particles of Radium-224 retainably embedded on or beneath a surface of the probe ensuring the particles remain in the probe while a therapeutic dose of decay chain radionuclides and alpha particles of said particles of Radium-224 leaves the surface, particles of Thorium-228 retainably embedded on or beneath the surface ensuring the particles of Thorium-228 remain in the probe while a therapeutic dose of decay chain radionuclides and alpha particles of said particles of Thorium-228 leaves the surface, wherein an activity level of the particles of Thorium-228 is lower than 50% of an activity level of the particles of Radium-224 in the device.
Across the independent claims, inventive coverage centers on coupling a first alpha-emitting isotope to a seed base with a quantified fraction leaving without radioactive decay and with daughter nuclei released upon radioactive decay, implementing a two-layer coating arrangement on a seed such that a first layer prevents passage of Radium-224 or Radium-223 while a second layer allows diffusion of at least 0.1% of radionuclide particles, and embedding Radium-224 and Thorium-228 within a probe so that each parent remains while therapeutic decay chain radionuclides and alpha particles leave the probe surface, with Thorium-228 activity maintained below 50% of Radium-224 activity.
Stated Advantages
Improves therapeutic energy distribution by allowing a controlled fraction of alpha-emitting parent radionuclide atoms to desorb/diffuse into nearby tumor tissue.
Limits escape of the radionuclide into healthy tissue.
Documented Applications
Brachytherapy delivery in a body of a subject using a seed base or a probe adapted for being at least partially introduced into the body.
Treatment where seed layout and different seed release rates are selected based on tumor properties including tumor size/shape.
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