Use of radio-pharmaceuticals as Therapeutic agents Flashcards
Describe radio-nuclide therapy
Systemic treatment.
Molecule labelled with a radio-nuclide delivers a toxic level of radiation to target disease sites.
Kill directly targeted cells +/- cross fire / bystander / abscopal effects
Treats primary tumour site and cancer that has spread throughout the body
Maximising the effectiveness of a treatment
High target concentration, minimising uptake in normal tissue
Emissions only irradiate tissue in the immediate target area
Abundant charged particles, energy deposited in a very small volume
Lack of penetrating gamma or x-rays; small amount can be useful for imaging.
Ideal therapeutic radiopharm
Half life: long enough to manu and transport, consider rate of uptake, metabolised, excretion
Chemical nature: - tumour specific agents
Biodistribution:
- degree of dilution, cell trans
- loc & blood supply of cells with affinity
- Agent metabolism / eliminated from body
How to maximise uptake
1) Choice of injection site
2) Incorporate radnuc to target
3) Consider drugs impact on biodistribuition
What restricts the use of radiotherapy ?
Radiotherapy limited by the dose to normal tissues
May take many months for serious damage to become apparent.
Must consider radio-sensitivity of cells
Describe radio-iodine therapy
Radioiodine highly selective irradiation of thyroid gland: 60% of administered 131I is taken up by thyroid. beta emission.
Benign dose: 300 – 550 MBq – Outpatient restrictions
Ablation dose: 1110-3700 MBq - Inpatient
Describe radium therapy
Bone metastases treatment
Primary bone tumours increased metabolic rate: Fast turnover of radiopharmaceutical
Shortlived high dose treatments helpful - mostly alpha
6 Ra doses via intravenous injection at four weekly intervals. doses based on patient weight.
Describe Radiolabelled peptides
Peptides: molecule of amino acids, smaller than proteins
Bind to specific cellular receptors which are involved in intra or inter cellular communication.
Describe somatostation treatment
Somatostatin analogues, in particular octreotide provide cancer treatment
Many tumours express somatostatin receptors Benign tissue does not.
Higher uptake in tumour compared to background tissue.
177Lu-Somatostatin DOTATATE, DOTATOC
Describe treatment of NETs
Neuroendocrine tumours
Concentrated in normal and abnormal sympathetic adrenergic tissue
123I and 131I MIBG taken up by the adrenal medulla and other tissues of the sympathetic nervous system
Not metabolised – excreted in urine
Describe Radioimmunotherapy
Attaches radiation to the monoclonal antibody.
Describe the crossfire/bystander effect
Radiation kills the surrounding tumour cells, not just the cells the monoclonal antibody attaches to - ‘crossfire’ or ‘bystander’ effect.
Describe SIRT
Selective Internal Radiation Therapy (SIRT)
Used for liver tumours 90Y micro-spheres
Lodge in arterioles in the growing rim of the tumour
Too large to pass through capillaries into venous system
High tumour dose, Low dose to healthy liver
Works because the tumour uses a diff blood supply to the liver. ID via angio with 99Tc MAA
