RADIOTHERAPY Flashcards
how radiation causes genetic mutations
- ionizing radiation strikes electrons in the body, freezing them from the atoms they were attached to
- the free electrons may hit and damage DNA directly
- free electrons may hit a water molecule, producing a free radical, a group of atoms that have an unpaired electron and is highly reactive. the free radical may then react with DNA and damage it
the effects of ionising radiation
- radiation effects range from complete breaks of DNA, to point mutations, radiation induced chemical changes in the nucleotides
- single strand DNA lesions do not cause chromosome aberrations
- DNA double breaks are the cause of chromosomal aberrations - very hard to repair
radiation therapy
- uses high-energy radiation to kill cancer cells by damaging their DNA
- can damage normal cells as well as cancer cells
types of radiation therapy
- machine outside the body (x-ray radiotherapy)
- radioactive material placed in the body near tumour cells (brachytherapy)
- radioactive molecules (radiopharmaceuticals) injected into the blood stream
dose fractionation
- radiation delivered in bundles
- fractionation allows normal cells to repair and survive but cancer cells can’t
- reduced radiation induced toxicity to non-cancer cells
radiation therapy dose
patients treated curatively with radiotherapy generally receive around 2 Gy per day, 5 days a week, for 5-7 weeks
intensity modulated radiation therapy (IMRT)
- a specialised form of 3D-CRT
- involves the use of varying intensities of hundreds of small radiation beams “beamlets” to produce dosage distributions
- beam is fitted to the tumour to avoid tissue toxicity
2 types of brachytherapy
interstitial therapy
contact brachytherapy
interstitial therapy
radiation sources are placed directly in the target tissue of the affected site, such as the prostate or breast
contact brachytherapy
radiation sources are placed in a space next to target tissue
radiotherapy side effects - acute phase
acute mucosal inflammation
- oesophagitis
- enteritis
- proctitis
- radiation dermatitis
- procedural pain - inserting brachytherapy
radiotherapy side effects - late phase
radiation fibrosis syndrome
- oesophageal stricture
- abdominal pain - bowel spasms
- non-bacterial cystitis
- strictures - bowel, anus, urethra
fatigue everyday
therapeutic differential in radiotherapy
- kill more tumour cells than normal tissue at lower doses
- but some cells are more resistant than others
radiosensitiser
- a drug that makes tumour cells more sensitive to radiation therapy
- down-regulated free radical scavengers so cancer cell bombarded with DNA damaging free radicals - sustains too much damage and dies
nuclear medicine
- application of radioactive substances in the diagnosis and treatment of disease
- allows detection of problems without invasive procedures
- to diagnose cancer a radioactive drug goes to the tumour, properties of the radiation allow a PET scan to be taken and show the cancer
scans to diagnose cancer
PET scan
MRI
CT scan
SPECT
theranostics
term used to describe the combination of using one radioactive drug to identify (diagnose) and a second radioactive drug to deliver therapy to treat the main tumour and any metastatic tumours
targeted radionuclide therapy
- selective radiation dose delivery
- as high a dose for the tumour ONLY
- as a tumour grows it changes, it upregulates some markers, makes new proteins or transporters which are not on the normal cells
- use molecules which have an affinity only for tumour cells
radionuclides
- can be produced artificially
- usually by the bombardment of stable nuclei by high-energy particles
- radionuclides can be chemically incorporated into another compound and injected into the body for diagnostic purposes - radiopharmaceuticals
radiopharmaceuticals contain
- a targeting part - seeks out the tumour
- the warhead - has the isotope on it
diagnostic imaging and treatment with 131I-MIBG
neuroblastomas express this transporter
what is radioimmunotherapy
- RIT uses an antibody labelled with a radionuclide to deliver cytotoxic radiation to a target cell
- in cancer, an antibody with specificity for a tumour-associated antigen is used to deliver a lethal dose of radiation to the tumour
how is immunotherapy specific towards tumour cells
RIT requires a tumour cell to express an antigen that is unique to the neoplasm or is not accessible to normal cells
2 radio labelled antibodies used to treat non-Hodgkin’s lymphoma
Ibritumomab tiuxetan (Zevalin)
Bexxar
Zevalin
- approved in B-cell non-Hodgkin’s lymphoma
- 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 or Yttrium-90
- targeted therapy - CD20+ cells (B cells and lymphoma) are killed by beta emissions from radioisotope
side effects of Zevalin
common s/e: fever, chills, rash, itching, dizziness, swelling
serious s/e: myelotoxicity
possible mechanisms of radio-immunotherapy tumour killing
- apoptosis - triggered by the antibody
- complement-dependent cytotoxicity (CDC) - antibody fixes complement that kills the tumour cells
- anti-dependent cellular cytotoxicity (ADCC) - where immune cells kill the tumour cells
- ionizing radiation from the radioisotope damages the tumour cells, leading to cell death
- vaccine-like effect - leading to adaptive immunity against cells that may initially survive
how long are patients radioactive after receiving intravenous MIBG (radiopharmaceuticals)
4 days
where are radiopharmaceuticals administered to patients
lead lined rooms
not in hospital ward because patient is radioactive
radio pharmacology
the study and preparation of radiopharmaceuticals
2 processes in the production of radiopharmaceuticals
- the production of a radionuclide on which the pharmaceutical is based
- the preparation and packaging of the complete radiopharmaceutical
