SUMMARY

INTRODUCTION

MATERIALS AND METHODS

MATERIALS AND METHODS (CONT.)

RESULTS

CONCLUSIONS

TEAM MEMBERS: Daniel Evans, Derek Dodge, Lisa Deconti, Rahul Vachhani

REFERENCES

Photodynamic Radiotherapy based on Constructive Interference of X-Ray Beams

● Our idea is to deploy multiple lasers that are all aligned in such a way as to constructively connect in one single point deep within the tissue. The individual lasers would all be weaker than necessary to kill any sort of malignant tumor. In fact it would be too weak to kill or damage any sort of tissue within the body. But when all of the lasers converge onto a single spot, the waves will align into a point laser powerful enough to damage the tissue but only in that point. This will eliminate or at least sufficiently limit the amount of collateral damage to surrounding tissues.

● We came up with two methods of treatment for tumors deep in tissue without having to make incisions on a patient: photodynamic treatment and external beam radiotherapy

Figure 3: Laser light activation of photodynamic drug and the reactions in the tumorThe drug is made of an artificial Bioactive Mediator which tags the cells for the immune system to destroy.

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Figure 1: The laser beams above have maximum energy and amplitude at the point of intersection.

Laser beam 1

Laser beam 2

Maximum radiation x ray delivered at point of intersection

Figure 2: Example of laser beams providing maximum radiation to tumor but less radiation everywhere else

Figure 5: Simple x ray schematic

We will use a combination of two methods of cancer and tumor treatment.

First Method: Photodynamic Treatment● Photodynamic therapy is the process of injecting a drug in the body that will stay in the cancer or tumor cells

longer than the healthy cells of the body. Once the drug is only left in the cancer cells, a light is shined over the cancerous area. This light activates the drug which breaks down the cancer cells.

● Since visible light is used, it cannot penetrate very deep into tissue. [7][5]● This method is good for non invasive treatment of skin cancer and tumors only a few millimeters beneath skin.

Second Method: External Beam Radiotherapy● External beam radiation is used to treat tumors deep in tissue.● Multiple treatments are given; usually in increments of 2 Gy per day, 5 days a week for 6 weeks [17].● This treatment kills surrounding cells and fast growing cells as well.

Taking pieces from both methods will allow us to create the best possible treatment for non invasive radiotherapy. Our goal from this is to:

● Limit traditional forms of collateral damage to surrounding cells via radiation and surgery● Leave the patient with no incisions or burns from treatment which are common in other treatments● Minimize risk of infection due to no incisions● Reduce recovery time from to surgery and chemotherapy● Limit the necessity of other forms of treatment and cut down the cost of treatment

Figure 4: Patient being prepped for External Beam Radiotherapy. The machine can rotate to achieve the best angle and position for treatment

Method 2: External Beam Radiotherapy● If we could focus these x rays into a beam of any thickness depending on the size of the tumor, our

treatment would be much more effective to kill tumors and keep surrounding cells alive.● One major problem with radiotherapy today is the fact that cells surrounding the tumor are often killed by

the radiation. Doctors and the mathematicians behind the radiation machines do the calculations to focus the beam as best they can but it is not always perfect.

● If a laser could be created with a desired thickness, much of the uncertainty in the radiation would be eliminated.

● Assuming that the points above are possible, intersecting multiple lasers of x ray radiation over a tumor at any given location would be simple. At this point of intersection there would be maximum radiation delivered to the tumor, but minimal radiation to anywhere else that the lasers are going through as seen in Figure 1 and 2.

● We will have to assume that we will only get constructive wave interference when we add the energies of the lasers together and the maximum energy of the waves will be:

Emax = E1 + E2 for 2 lasers intersecting at any angle [1],[2],[11],[17]

Until X ray lasers become more developed and more understood, we think the photodynamic method would be better treatment for now. Both treatments are currently very expensive. Pure radiation therapy can range anywhere from four to fifty five thousand dollars for an entire treatment [6]. The PDT drugs alone can cost close to three thousand dollars for a full prescriptions worth [1]. But by using our method, we hope:

● combining both treatments would result in our method most effectively ● our method focuses on the middle class citizens (majority of the population, more affordable, no need to rely on

health insurance as much

Future work: MRI activated nanocapsules with photodynamic type drug [3].● no need of using x ray radiation but use magnetic fields from MRI (safer but expensive)● magnetic fields have far less side effects compared to radiation ● when MRI are more common in treatment use, prices will decrease for treatment (future)

Summary:We would create a drug that is activated by x rays since we know these penetrate deep into the body without much harm at low doses. We would focus multiple x rays into lasers and intersect these lasers over the tumor resulting in maximum radiation at the point of intersection only, this would allow us to use safe doses of x rays in each laser but at the point of intersection the dose would be higher due to the sum of the energies (amplitude of the waves). This would activate our photodynamic drug that is located in the tumor to destroy the tumor.

Most x ray machines use a tungsten-rhenium target / anode on a molybdenum core, backed with graphite for heat shielding in the machine itself. When hit with electrons, the tungsten target will give off x ray radiation. This process of creating x rays is most efficient when the elements inside the x ray tube are in a vacuum. A tungsten anode is used because of its high photon energy compared to other heavy metals that would give off x rays. Since the medical field uses tungsten in their x rays, we would as well in both of our methods of treatment. Both of our methods also use the idea of constructive wave interference as seen in Figure 8. [1][6][10][16]

Method 1: Photodynamic Therapy● Photodynamic therapy is only used to treat cancer and tumors a few millimeters beneath the skin or surface.● The drug or photodynamic agent commonly used in deep tumor treatment is called Haematoporphyrin (HpD)

which reacts to 1064nm light also known as the Nd:YAG laser. The patient still needs to be cut open with this current method. The Nd:YAG laser also makes incisions in the patient as it activates the HpD.

● Many other photodynamic agents are available that react to different wavelengths of light and thus have different depths of penetration. Common examples of such agents include Photofrin®, ALA or Levulan®, and Metvixia®

● Once light has been shone on the area which contains a photodynamic agent, then the agent is “activated”.● When the photodynamic agent is activated, the structure is changed and it becomes a molecule which breaks

down almost all proteins including the cell’s DNA and in turn killing it.● We would use this same idea but create a drug that is activated by an x ray. We would do this since it is already

known that x rays can penetrate deep into tissue and sometimes through bone depending on the wavelength and photon energy.

● This method would require far less amounts of x ray radiation since we only need to activate a small dose of a drug in a tumor with the beam.

● This is better than the prolonged period of radiation the patient would be exposed to if they were trying to kill the tumor by exposure, without the help of the drug. [5],[7],[13]

Figure 6: Wave interference with no phase shift

Figure 7: X Ray laser beam machine

Figure 8: Flexible laser fiber bronchoscope Nd:YAG laser

Equation 1 Emax = E1 + E2 maximum energy at point of intersecting lasers equals the sum of the energies of each laser

Equation 2 utotal = uE + uBtotal energy in an electromagnetic wave is the sum of the electric field energy and magnetic field energy

Equation 3 uE = ½ε0E2 energy in an electric field

Equation 4 uB = (B2 ) / (2μ0) energy in a magnetic field

Equation 5 E = ε0 sin(ɷt - kx) electromagnetic wave (assume no phase shift; k = 0)

Equation 6 B = B0 sin(ɷt - kx) electromagnetic wave (normal to equation 5)

Equation 7 ɷ = 2πf angular frequency = 2π times frequency

Equation 8 u = hf minimum energy of an electromagnetic wave is Planck’s constant times frequency

Equation 9 p = hf/c momentum of electromagnetic wave equals Planck’s constant times frequency divided by speed of light

Figure 9: Tumor growth delay after photodynamic therapy and radiotherapy comparatively

Figure 10: Possibility of survival vs time after radiotherapy alone and radiotherapy with chemotherapy

In both Figures 9 and 10, radiotherapy alone was not as effective as radiotherapy along with photodynamic therapy or chemotherapy. Temozolomide is a drug commonly used in chemotherapy given to patients orally. Overall, the drug breaks down the proteins and DNA of the cancer similarly to photodynamic therapy. Since we conclude that adding a drug to radiotherapy is better for the patient, we can say that photodynamic agents would be the best method of treatment since they are only present in the cancerous cells at the time of treatment. This would minimize the side effects of chemotherapy. To ensure our photodynamic agent gets activated deep in the body, our drug will need to be x ray activated since we know that x rays can penetrate deep into the body. If these x rays were focused in multiple laser beams, then we could intersect the laser beams over the tumor to activate the drug with maximum energy over the tumor and minimum energy everywhere else the laser touches.[17]

Common Electromagnetic Wave Equations Needed for Further Analysis

Using the equations above we could calculate energies and power needed for treatment (eq. 1 - 6) along with some absorption (Eq. 9). We would need to perform an absorption spectrum to optimize the best wavelength with maximum efficiency of delivering radiation but also providing enough penetration deep into tissue and bone.