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Summary of Lesson 4 'Radiopharmaceuticals'
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This document includes the summary of Lesson 4 of the course “Nuclear biomedical imaging, preclinical and clinical studies with a focus on oncology.”
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Lecture 4: 24/11Development and applica/ons of radiopharmaceu/cals
Radiopharmaceu-cals
- Radiopharmaceu.cal: medicinal product fused to one or more radionuclides, meets
all the standards set for nonradioac.ve pharmaceu.cals
- Radionucleo.de is unstabel -> decays with a specific rate = 1/2
- Difference between SPECT/PET and therapy
o SPECT/PET: leaves body
o Therapy: compounds have more energy travel a small distance, stay in the body -
> toxic
- Nmol-pmol
- Have a drug = key for a target in the body -> high specificity
- Provide new informa.on about the disease
o To use for diagnosis
o Assessing effec.veness and ac.on of therapy
§ Evaluate the toxicity
§ Visualise a target for what the therapy exist
Development of radiopharmaceu-cs
Target
- Know link between target and specific pathology
o Dopamine receptors -> movement disorders
o PSMA -> prostate cancer
§ To iden.fy prostate cancer, can also be used as a target
o Amyloid plaques -> Alzheimer’s disease
è Image target for diagnosis or for drug development, visualize role of target
- Unknow link between target and specific pathology
o You want the visualize the role of the target and the role of the pathology
è Image target to inves.gate specific pathology; develop new treatments
- Type of targets
o Receptors
, o Transporters
o Enzymes
§ You can image the ac.vity of the enzymes to see if the treatment works or
not.
§ Tracers that target the acetylcholinesterase you can visualize the enzyme
and the role
o Immunologic role
§ An.body radiolabeled
§ Pep.des that target a specific an.gen
§ HER2 receptor abnormal expressed in breast cancer cells -> an.body
targe.ng the receptor -> use to diagnose and can be used to determine
which pa.ents will react on an.body therapy and which pa.ents will not
respond
Vehicle
- An.body
o Larger molecules
o Slows down the prolifera.on of the cancer
o Accumulate a larger part, more slowly
- An.body fragments
o Smaller parts
o Nanobody of the an.body against the target
o Accumulate faster, more deeply
o Clear faster
- Small molecules specifically prepared via organic chemistry
o You can op.mize target affinity, specificity, circula.on, stability proper.es
Radioisotope
- Cell expressing the HER2 receptor with an an.body
- Choise depends on:
o Difference depends on the half life of the radioisotope
§ A radionuclide that labels an an.body should have a big difference of a
radionuclide labeling a small molecule
§ Radiopharmaceu.cals are unstable and decay with a specific half life
• The half life should be matched with the biological half life of the
target
o Applica.on: therapy of diagnosis (PET or SPECT)
o Availability: mode of produc.on
- There are different isotopes
o Depending on the par.cles that are emi]ed
o B+ = positron emission in the nucleo.de
§ Selec.on to define which radionucleo.de goes with your tracer
§ You also have the think about the place where it is produced and where it
is needed
o SPECT isotopes
§ Longer half lives, not always
§ Can be kept for a longer .me
§ Detect with a SPECT camera
o Therapy
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