Making Alpha Therapy Possible

TARGETED ALPHA THERAPY

Cancer treatments have evolved significantly in recent years and the focus of current clinical research studies is on developing more targeted therapies. Today, targeted radiotherapies only make use of so-called Beta-isotopes. Novel and breakthrough clinical research has proven that targeted therapies using Alpha-isotopes can be much more effective.

  

TARGETED THERAPY

CANCER TREATMENTS

When treating cancer patients, oncologists currently have a few treatments at their disposal. Of these treatments, surgical intervention, chemotherapy and nuclear medicine are likely to remain a continued treatment of cancer. However, more recent clinical research has focused on developing more and more Targeted Therapies. These therapies use chemicals, drugs, toxins or radioactive substances to change the way cancer cells grow, divide and spread.

INVISIBLE CRUISE MISSILES

In Targeted Therapy a therapeutic agent is loaded on a targeting molecule/ monoclonal antibody (see it as an almost invisible cruise missile loaded with a war head) and is inserted into a patient's bloodstream where it automatically finds, attacks and destroys the malignant cells, while leaving the healthy tissue surrounding the tumor and rest of the body largely unaffected. The cruise missiles can be loaded with a range of war heads. For example, it can be loaded with a chemical war head (Targeted Chemo Therapy) or with a nuclear war head (Targeted Radio Therapy). Unfortunately all these therapies cause peripheral damage to healthy tissue by provoking mutations in neighbouring cells that may ultimately result in the reoccurrence of the cancer.

ALPHA THERAPY

Nowadays, radioactive targeted therapies only make use of so-called Beta-isotopes. However, novel and breakthrough clinical research has proven that targeted therapies using Alpha-isotopes are much more effective in actually destroying the cancer cell and significantly limiting damage to surrounding healthy tissueWe speak of Targeted Alpha Therapy, or TAT, when Alpha-isotopes are loaded on an targeting molecule/ monoclonal antibody. 

 

ALPHA- VERSUS BETA-ISOTOPES

DOUBLE-STRAND DNA BREAKS TO DESTROY THE CELL

Double strand DNA break

Alpha isotopes have more focus and cell killing power than a Beta isotope. The best way to destroy a malignant cancer is to completely eliminate each cancerous cell that makes up the cancer by disrupting and breaking its DNA. Alpha particles are more effective than other types of radiation (see bottom of page) at causing double-strand breaks in DNA molecules, thereby causing the cell to die. (See below for a simple explanation of the differences in energy levels of Alpha- and Beta isotopes.)

ALPHA ISOTOPES HAVE MORE CELL KILLING POWER AND FOCUS

Outside of the body, Alpha radiation is the least dangerous form of radioactive radiation for human beings. This is because Alpha radiation, contrary to Beta radiation, does not penetrate the skin. However, Alpha radiation can be lethal for a malignant cancer cell. The energy dissipation (i.e. the "cell-killing power") of an Alpha-isotope is 12.500 times that of a Beta-isotope. In addition, the radiation radius of an Alpha-isotope is 5 cell-diameters as compared to several hundred of a Beta-isotope. Consequently, Alpha-isotopes have superior “focus” and “cell-killing power” compared to the currently used Beta-isotopes. Nonetheless, its application in the treatment of cancer is not yet common practice.

ENERGY LEVEL OF AN ALPHA VS A BETA

To understand the differing energy levels of Alpha isotopes versus Beta isotopes, you can compare them with billiard balls and ping pong balls. Imagine firing a ping pong ball at a cluster of billiard balls. As you can understand, the size and weight of a singular ping pong ball has little effect on the heavier billiard balls. To move the cluster of billiard balls, many ping pong balls are needed. This is Beta-radiation. Now imagine replacing the ping pong ball with a billiard ball. Firing a single heavy billiard ball at the same cluster of billiard balls immediately disrupts it and causes the balls to separate and shoot off in multiple directions. This is Alpha radiation.

 

ACTINIUM-225 and BISMUTH-213

Isotopes Ac-225 & Bi-213

An obstacle for use of Alpha isotopes in mainstream cancer therapies is the long half-lives of almost all Alpha-isotopes. These can lead to toxicity problems and patients being exposed to radiation long after the malicious cells have been eradicated. However, an unique tandem of two Alpha-isotopes are an exception to this problem:

Actinium-225 or Ac-225 with a half-life of 10 days, and

Bismuth-213 or Bi-213 with a half-life of 46 minutes

Both compounds have exceptionally short half-lives. Moreover, Actinium-225 and Bismuth-213 have a superior ability to bind to currently known organic molecules used as delivery systems in targeted cancer therapies. During its half-life cycle, Actinium-225 organically decays into the alpha isotope Bismuth-213. Bismuth-213 in turn has a half-life of only 46 minutes, making it the ‘isotope of choice’ for the clinical treatment of cancer.

 

ALFARIM WILL PRODUCE AND SUPPLY ACTINIUM-225

With a half-life of 10 days, Actinium-225 offers the solution in overcoming the logistical challenge to delivering the preferred Bismuth Alpha-isotope to the patient’s bedside. However, a lack of readily available Actinium-225 represents a substantial bottleneck in the further clinical development of Alpha-Isotope based targeted therapies. Globally, there are currently 13 Alpha-Immuno based clinical development projects and a significant number of clinical research initiatives held up due to a scarcity of predictable quantities of Actinium-225.

AlfaRim has developed a proprietary and IP protected production process for the predictable supply of large quantities of Actinium-225 at acceptable prices for the application of Alpha radiation in mainstream cancer therapies. This breakthrough by AlfaRim to harness the predictable supply of large quantities of Actinium-225 will:

  1. Allow existing clinical research initiatives on Targeted Alpha Therapy to come into maturity, and
  2. Open the way towards Targeted Alpha Therapy becoming a mainstream therapy for the treatment of many types of cancer.

 

BASIC INTRODUCTION TO RADIATION

Radiation comes in a few forms: Alpha-, Beta- and neutron particles, and gamma- and X-rays. All types are caused by unstable atoms, which have either an excess of energy or mass, or both. To reach a stable state, these atoms release energy or mass in the form of radiation.

ALPHA RADIATION

Types of radiation

The least dangerous radiation is called Alpha radiation (or, with a Greek symbol, α-radiation). This radiation is caused by alpha decay. This happens when an atom loses two protons and two neutrons at the same time and turns into another atom. The two protons and neutrons together form an 'α-particle', and that α-particle is shot away as a projectile. Alpha particles are relatively large and heavy and are thereby able to quickly destroy other particles. However, since they are large and heavy (travels not more than 1-2 meters through the air) it also means that α-particles are easily stopped by other particles and are unable to penetrate other material such as skin or paper. For humans, alpha radiation is as good as harmless, because it can never penetrate far enough to cause major damage to tissue. However, it is dangerous to swallow or inhale a source of α-particles (but why would you do that?). The particles would then touch the inside of the body where there is no protective layer of skin.

BETA RADIATION

Beta radiation (β-radiation) occurs at beta decay when in the nucleus of an atom a neutron changes itself into a proton and turns into another atom. When a neutron becomes a proton, an electron is formed which shoots away as a projectile. An electron is about 7.500 times lighter than an Alpha particle and causes much less damage. Nevertheless, Beta radiation is more dangerous than Alpha radiation. This is because Beta particles are much smaller and able to penetrate much deeper. As a result, they can also cause a lot more unintended damage.

GAMMA RADIATION

The most dangerous type of radioactive radiation is Gamma radiation (γ- radiation). Gamma radiation does not consist of particles, such as Alpha- and Beta-radiation. It consists of powerful electromagnetic rays. A nucleus which is in an excited state may emit one or more photons (packets of electromagnetic radiation) of discrete energies. The emission of gamma rays does not alter the number of protons or neutrons in the nucleus but instead has the effect of moving the nucleus from a higher to a lower energy state (unstable to stable). It's very difficult to stop gamma radiation (thick plates of lead and concrete is commonly used). Therefore, it’s extremely harmful to humans.

  

ABOUT ALFARIM

AlfaRim Medical Holding BV is a Dutch privately-owned limited company originally founded by globally recognized "Father of Actinium" Dr. Ir. Maurits Geerlings. Learn more about what drives us and meet our team. Read more

ABOUT ACTINIUM-225

Actinium-225 is an isotope of Actinium and is used in nuclear medicine in the treatment of cancer. Actinium-225 itself and its decay products emit alpha particles which destroy cancerous cells in the body. Read more

ABOUT ALPHA THERAPY

Today, targeted radiotherapies only make use of so-called Beta-isotopes. Novel and breakthrough clinical research has proven that targeted therapies using Alpha-isotopes can be much more effective. Read more