Company: DRTSW
Filing Date: 2025-03-12
Form Type: 20-F
Source: 0001213900-25-023187
Chunk: 117

Company: Alpha Tau Medical Ltd.
Filing Date: 2025-03-12
Form: 20-F
Item: Item 4
Chunk 117
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 that can pass longer distances and are attenuated over lengths, depending on the medium being traversed.

Radioactivity involves spontaneity,
with high radioactivity corresponding to high likelihood of sporadic emissions towards stabilization. Clinical application of the emitted
energy-the alpha particles, beta particles and gamma rays-from a radioactive source therefore demands the controlled harnessing of a spontaneous
phenomenon, but with some predictable, key parameters, towards a specific desired outcome.

Mechanisms of alpha, beta, and gamma
radiotherapy

Radiation, when aimed towards
the destruction of cancerous or other damaged cells in the body, is known as radiotherapy. Depending on the patient’s particular
condition, radiotherapy can be either an alternative or a complement to surgery or systemic therapies for the treatment of cancer.

Cell death induced by radiotherapy
can occur either through direct or indirect DNA damage. Alpha particles generate direct DNA damage, while beta particles and gamma rays
destroy cancer cells primarily when they encounter oxygen: specifically, they rely on the presence of oxygen which, upon impact from the
beta or gamma radiation, forcefully ejects electrons in a process known as ionization, wherein these atoms, now excited with unpaired
electrons, become free radicals which are highly reactive. While the beta or gamma radiation will have little direct impact on the cells,
the highly reactive free radicals will react with cellular machinery, including a strand of DNA should they encounter one, generating
a single-strand break in the DNA. This is often a short-lived success, however, as the cancer cell may be able to reconstitute or repair
the DNA damage after single-strand breaks, depending on its current position in the cell cycle. By contrast, alpha-emitters, with hundreds
of times the linear energy transfer rate of beta-emitters, and alpha particles’ heavier mass and far shorter particle paths (less
than 100 μm) relative to beta particles’ lighter mass and lengthier (up to 12 mm) path, generally destroyed radioresistant
cells more effectively than other forms of radiation such as photons (e. g. X-rays) in pre-clinical studies - causing multiple, irreparable,
DNA double-strand breaks and other cellular damage upon directimpact - within a very short distance. Alpha radiotherapy has approximately
500x more concentrated cytotoxic potency than beta particles, with radioactive potency that attenuates as they travel. Beta and gamma
radiation are inherently limited in their use in radiotherapy, as their weaker potency and their