Lecture 6 - radiotherapy

Question 1

what is ionising radiation ?

Answer 1

Ionizing radiation hits the body, knocking electrons loose.
* These free electrons might hit and harm DNA directly.
* They might also hit water molecules, creating highly reactive groups of atoms called free radicals.
* These radicals can then react with DNA, causing damage.

Question 2

what are consequences of ionising radiation?

Answer 2

ionising radiation can cause DNA breaks in strands, to point mutations, where radiation induces chemical structural changes in the nucleotides. single DNA breaks are often not a problem in chromosomes because 90% of lessons are repaired in less than an hour. double DNA breaks are more difficult to repair, therefore are the main cause of chromosomal problems

Question 3

what are key points of radiation therapy for cancer?

Answer 3

Radiation therapy of cancer involves directing a high-energy radiation to kill cancer cells by damaging their DNA

radiation therapy can affect normal cells as well as cancer cells, therefore, requires planning to minimise side effects

the dose of high energy radiation for normal cells to safely receive is known for all tissues of all body parts

radiation theory can be received via a machine outside the body - external beam therapy, by placing a radioactive material close to the tumour cells - brachytherapy, or by injecting radioactive materials into the bloodstream.

radiotherapy may be given before, during or after surgery, depending on the cancer type

radiotherapy may be given alone, or in combination with chemotherapy agents

Question 4

what does external beam therapy use?

Answer 4

external beam therapy include linear accelerators (Linacs) that generate high-energy X-rays and gamma rays, as well as proton therapy that utilizes positively charged particles.

Question 5

how is radiotherapy delivered?

Answer 5

radiotherapy is not delivered all at once but in fraction.
fractionation allows normal cells to repair and survive but cancer cells do not do this
reduced radiation induces toxicity to non-cancer cells

Question 6

what are specialised types of external radiotherapy?

Answer 6

intensity modulated radiation therapy uses is a specialised form of 3d-crt.

the beam if fitted to the tumour, in manner that is conformational to the tumour cell. this reduces the toxicity dose being targeted at healthy cells, so less damage to the normal cell.

Question 7

what are 2 types of Brachytherpay?

Answer 7

interstitial brachytherapy is when the radiation source is placed into the target tissue of the affects site such as breast or prostate

contact brachytherapy is when the radiation source is placed in a space next to the the target tissue

Question 8

what are side effects of radiotherapy?

Answer 8

acute phase - acute mucosal inflammation: oesophagititis, enteritis, proctitis,
radiation dermatitis
procedural pain

late phase - radiation fibrosis syndrome, oesophageal stricture, abdominal pain: bowel spasms, and non bacterial cystitis

Question 9

how can radiotherapy and chemotherapy be used together?

Answer 9

a radio sensitiser is a drug that makes tumour cells more sensitive to radiation therapy. it inhibits repair so cancer cells sustains too much unrepaired damage and dies. a radiosensitizer downregualtes free radical scavengers so there is more DNA damage by free radicals and so cell dies

Question 10

what is nuclear medicine?

Answer 10

nuclear medicine is the application of a radioactive substance in the diagnosis and treatment of cancer, without using invasive procedures. to diagnose cancer,a radioactive drug with very low radioactivity is given to the patient, which travels down into the tumour. properties of radiation allows a picture to see the cancer or tumour growing.

Question 11

what are different scans used to detect cancer?

Answer 11

PET scan
MRI
CT scan
SPECT

Question 12

what is the purpose of using different scans for imaging?

Answer 12

1. to diagnose the cancer or metastases
2. to make informed decision treatments

we want a selective radiation dose delivered that has targeted therapy. this means we want to achieve as high dose as possible to the tumour only and low dose as possible to the normal cells. to d this we need a targeting agent that affects the tumour only

Question 13

what is theranostics?

Answer 13

theranosctics is a term that refers to the diagnosis and therapeutics.
theranostics is when a combination of one radioactive drug is given for the diagnosis and another radioactive drug is given to deliver theory to the main tumour or metastases

Question 14

what is targeted radionuclide therapy?

Answer 14

Targeted radionuclide therapy is the use of molecules that only have affinity for tumour cells.
for example
targets proteins only expressed on tumour cells
targets rapid cell division of tumour cells over normal cells
targets transporters that only reuptake in tumour cells

some molecules are 131MIBG and NA131
radioimmunotherapy: when anti-tumour antibodies are conjugated with radionuclides.

Question 15

how are radionuclides made?

Answer 15

radionuclides can be made artificially
this is usually by the bombardment of stable nuclei by the high energy particles
radionuclides can be chemically incorporated into the compounds that is injected into the body for the purpose of diagnostics
the RP contains
1. targeting agent - seeks out the tumour
2. warhead - has the isotope on it

Question 16

what is needed for radiopharmaceutical?

Answer 16

For Radiopharmaceutical, we need
1. A delivery system that will take the radiation directly to the tumour cell
2. a warhead that once at the tumour cell, kills it directly with limited effect on surrounding tissues.

different isotope to target different characteristics depending on what we need to treat eg beta-emitter used for long path length and alpha emitter can be used for very short path length

Question 17

what are types of target for radionuclide therapy?

Answer 17

types of targets on cancer cells for radionuclide therapy are
Extracellular:

• Transporters - Radioiodine
• Neurotransmitter receptors
• Hormone receptors
• Neuropeptide receptors
• Growth Factor receptors
• TAA epitopes
• Intracellular
• Metabolic pathways
• DNA/RNA
• Other organelles
• Thyroid cancer expresses
  The sodium iodide symporter
  Its role is to take up iodine into
  the cell
  We can radiolabel this- its taken
  Up into the thyroid cancer cells

Question 18

describe diagnostic imaging and treatment with 131MIBG.

Answer 18

Neuroblastoma is a childhood tumour that occurs in young children and arises from neuroectodermal tissue. patient with stage 4 neuroblastoma has an adrenal pituitary tumour and lesions of the spine and femur.

neuroblastoma expresses the noradrenaline transporter which can take up 131MIBG noradrenaline analogue.

131MIBG has been found to be an effective single agent, have few side effects, palliation, long term remission and no long term cure.

Question 19

describe radioimmunotherapy

Answer 19

Radioimmunotherapy (RIT) uses an antibody labeled with a radionuclide to deliver cytotoxic radiation to a target cell.

In cancer therapy, an antibody with specificity for a tumor-associated antigen is used to deliver a lethal dose of radiation to the tumor cells.

The ability for the antibody to specifically bind to a tumor-associated antigen increases the dose delivered to the tumor cells while decreasing the dose to normal tissues.

By its nature, RIT requires a tumor cell to express an antigen that is unique to the neoplasm or is not accessible in normal cells
The benefit of RIT is that it can be used to image the
patients tumour and then to treat the cancer- theranostic

Question 20

what are 2 treatments for NHL?

Answer 20

Zevalin and bexxar :
zefalin
The drug ibritumomab tiuxetan (Zevalin®) approved by the Food and Drug Administration (FDA)
for the treatment of certain types of B-cell non-Hodgkin lymphoma (NHL).

The antibody recognizes and binds to a protein (CD20 molecule) found on the surface of B lymphocytes.

Conjugated to either the radioactive isotope Indium-111 (111In) or Yttrium-90 (90Y)

Targeted Radiotherapy
CD20+ cells (B cell and lymphoma) are killed by β emissions frommradioisotope

Common side-effects: fever, chills, rash, itching, dizziness, swelling Serious side-effects include myelotoxicity

Question 21

what are possible effects of radioimmunothrpay tumour killing

Answer 21

When radio-labeled antibody binds to tumor cells it can cause tumor killing by

Self-killing (apoptosis) - programmed cell death triggered by the antibody

(2) Complement-dependent cytotoxicity (CDC) - where antibody fixes complement that kills the tumor cells

(3) Antibody-dependent cellular cytotoxicity (ADCC) - where effector cells (immune cells) kill the tumor cells

(4) Ionizing radiation from the radioisotope damages the tumor cells, leading to cell death

(5) Vaccine-like effect - leading to adaptive immunity against cells that may survive initial

Question 22

describe how radiopharmaceutical are given

Answer 22

radiopahramceuticals cannot be given in a hospital ward as patient supine, poo, sweat clothes become radioactive. they are given to the patient in an lead lined room where the nurses go in briefly to avoid overexposure. the patin is given an IV MIBG dose where administration takes an hour and half but child is radioactive for 4 days. they will remain inform with limited contact during that time

Question 23

what is radiopahrmacology?

Answer 23

radiopahramcology is the study and preparation of radiopahramceitucals

radiopharmaceuticals are made by combining a small amount of radioactive material with a larger molecule that can work as a medicine in the body. the radioactive nuclide trace allows it to be detected with PET scan or gamma camera

Question 24

what is the main responsibility of radio pharmacists?

Answer 24

Radiopharmacist in nuclear medicine is the preparation of radiopharmaceuticals to ensure their safety and efficacy. involves the manufacture of sterile radioactive medicines. quality assurance and quality control testing form an important part of the responsibility. A major challenge is the development of new radiopharmaceuticals