DaRT Source Radon Release Control for Pancreatic Cancer

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Solution Overview

Problem

Current radiotherapy methods using alpha particles face challenges in delivering sufficient radiation to tumors while minimizing damage to healthy tissues, as the short range of alpha particles limits their therapeutic effectiveness and existing diffusion methods struggle to maintain adequate radon release rates within tumors.

Innovation Solution

The development of diffusing alpha-emitter radiation therapy (DaRT) sources with tailored radon release rates and spatial arrangements, such as hexagonal patterns with specific spacings, to ensure effective tumor coverage and minimize radiation exposure to healthy tissues, using radium-223 or radium-224 atoms to generate alpha particles with controlled diffusion and decay.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If alpha particles are used for radiotherapy, then the destructive effect on tumor cells is enhanced, but the short range limits the therapeutic effectiveness

Engineering Contradiction:
Improvedestructive effect on tumor cellsVSAvoidrange of alpha particles
Core Design Contradiction:
ReliabilityVSLength of moving object

Solution Approach 1:

The source is segmented into multiple discrete radium atoms distributed throughout the tumor volume, each generating alpha particles that travel short distances. This segmentation allows the tumor to be treated as a collection of localized treatment zones, overcoming the short range limitation by distributing multiple sources throughout the tumor.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Radon atoms serve as intermediaries that carry the radium's radioactive decay product away from the source into the surrounding tumor tissue. The radon atoms diffuse from the source location, delivering alpha-emitting radionuclides to distant tumor cells while the parent radium remains confined to the source.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Stability of the object's composition

If radium atoms are attached to the source with sufficient strength to prevent loss, then the source stability is improved, but the daughter radionuclides cannot leave the source to treat surrounding tissue

Engineering Contradiction:
Improvesource stabilityVSAvoidradon release rate
Core Design Contradiction:
Stability of the object's compositionVSProductivity

Solution Approach 1:

The source structure has different local properties: the radium atoms are strongly bound to the source matrix (preventing loss), while the daughter radon atoms are allowed to escape into the tumor tissue. This local differentiation in binding strength enables simultaneous source stability and radon release.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The binding energy parameter is changed between parent and daughter atoms. Radium atoms are bound with high binding energy to remain on the source, while radon atoms are released with lower binding energy to diffuse into the tumor. This parameter change enables selective retention of parent atoms and release of daughter atoms.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If the source releases too many radon atoms, then the tumor destruction probability increases, but healthy tissue outside the tumor is damaged

Engineering Contradiction:
Improvetumor destruction probabilityVSAvoiddamage to healthy tissue
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The harmful effect is extracted and localized to the tumor volume by confining the radium sources within the tumor boundaries. The short range of alpha particles ensures that even though radon atoms diffuse throughout the tumor, the alpha radiation does not extend beyond the tumor into healthy tissue.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The source activity is predetermined and calibrated to release exactly the right amount of radon atoms needed for tumor destruction. By controlling the initial radium activity and radon release rate, the treatment delivers sufficient radiation to destroy the tumor while preventing excessive radon release that would damage healthy tissue.

Inventive Principle:
Principle #9Preliminary anti-action

4Area of stationary object

If conventional radiotherapy is used, then the treatment coverage is extended, but the effectiveness against hypoxic cells is reduced

Engineering Contradiction:
Improvetreatment coverageVSAvoideffectiveness against hypoxic cells
Core Design Contradiction:
Area of stationary objectVSReliability

Solution Approach 1:

The hypoxic conditions that normally protect tumor cells from conventional radiation are converted into a benefit for alpha therapy. Alpha particles create dense ionization tracks that produce complex DNA damage independent of oxygen, turning the hypoxic environment from a protective factor into a condition where alpha particles maintain their full destructive effectiveness.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach allows for accurately tailored radiation delivery to tumors, increasing the therapeutic range of alpha radiation while minimizing damage to surrounding tissues, ensuring effective tumor destruction with controlled radon release rates and spatial distribution.

Implementation Method 1

radium-223 or radium-224 atoms, which generate chains of several radioactive decays with a governing halflife of 3.6 days for radium-224 and 11.4 days for radium-223

Methodology Applied
Scientific EffectRadioactive decay: Radioactive Decay

Implementation Method 2

These radionuclides, and their own radioactive daughter atoms, spread around the source by diffusion up to a radial distance of a few millimeters before they decay by alpha emission

Methodology Applied
Scientific EffectAlpha emission: Radioactive Decay

Implementation Method 3

These radionuclides, and their own radioactive daughter atoms, spread around the source by diffusion up to a radial distance of a few millimeters before they decay by alpha emission

Methodology Applied
Scientific EffectDiffusion: Diffusion

Data Source

PatentEP4101505A1Diffusing alpha-emitter radiation therapy for pancreatic cancer
Publication Date: 2022.12.14 ALPHA TAU MEDICAL LTD
  • EP4101505A1 patent drawingFigure 1
  • EP4101505A1 patent drawingFigure 2
  • EP4101505A1 patent drawingFigure 3~4

AI summary

A diffusing alpha-emitter radiation therapy (DaRT) source for use in treatment of a pancreatic cancer tumor of a patient, the source comprising a support having a length of at least 1 millimeter; and radium-224 atoms coupled to the support such that not more than 20% of the radium-224 atoms leave the support into the tumor in 24 hours, without decay, when the source is implanted in the tumor, but upon decay, at least 5% of daughter radionuclides of the radium-224 atoms leave the support upon decay. The administration pattern of the source comprises implanting the source in the pancreatic cancer tumor throughout the tumor, with a spacing between the sources of between 3-4.5 millimeters, and the radiation therapy source has a radon release rate of between 1.2 and 2.5 microcurie per centimeter length.