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aa Radiochemistry > Radioactive substances in medicine 3 > Flashcards

Radioactive substances in medicine 3 Flashcards

1
Q

What is PET

A
  1. Positron Emission Tomography
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2
Q

What are the radionuclides used in PET scanning and half lives

A
  1. 11C - 20 min
  2. 13N - 10 min
  3. 15O - 2 min
  4. 18F - 110 min
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3
Q

Describe radionuclides used in PET

A
  1. beta + emitting isotopes with short half-lives
  2. Cyclotron made
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4
Q

Describe how PET works

A
  1. Radio nuclei emits a beta+ which meets an electron and produces 2 gamma rays 180 degrees from each other
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5
Q

Describe 18F-FDG

A
  1. Taken up by cells and retained by tissues with high metabolic activity (diseased) such as the brain or most types of malignant tumours
  2. But low specificity
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6
Q

Describe production of PET tracers

A
  1. Can be produced in a cyclotron or in a generator
  2. During synthesis a radionuclide may be attached to a targeting molecule (antibody, protein, peptide etc) to develop an imaging agent
  3. After administration the imaging agent gravitates to the target
  4. The positrons released from the target travel in the tissue until they meet their anti-particle i.e. electron and a coincidence happens causing release of gamma rays
  5. PET camera is able to detect these gamma-rays and with mathematical image construction a 3D image is received
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7
Q

What is a difference between cyclotron and generator

A
  1. Cyclotron is relatively large
  2. Generator quite small
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8
Q

What is a positron mean free path

A
  1. Average distance travelled by this moving particle between successive collisions modifying its direction or energy/other properties
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9
Q

What happens after injection of a tracer compound labelled with PET isotope into a subject

A
  1. The subject is placed within the field of view of a number of detectors capable of registering incident gamma rays
  2. The radionuclide in the radiotracer decays and the resulting positron subsequently annihilate on contact with electrons after travelling a short distance within the body
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10
Q

Describe the path of positrons

A
  1. As they travel through human tissue they give up kinetic energy by Couloumb interactions with electrons
  2. Mass is about the same as electrons so may undergo large deviations in direction with each interaction
  3. Once at thermal energy they interact with electrons by annihilation which produces two photons (gamma rays) which are detected
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11
Q

Describe detection in PET

A
  1. PET camera detectors generate a timed pulse when it registers an incident photon
  2. Detector electronics are linked so two detection events (pulses) unambiguously occurring within a certain time window may be called a coincident and this be determined to have come from the same annihilation
  3. These events can be stored in arrays corresponding to projections through the patient and reconstructed using tomographic techniques
  4. Resulting images show tracer distribution throughout the body of the subject
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12
Q

What type of isotopes tend to decay by positron emission

A
  1. Proton-rich
  2. Proton in nucleus decays to a neutron, positron, and a neutrino
  3. Daughter isotope has an atomic number one less than the parent
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13
Q

Why are coincident gamma rays good

A
  1. No need for a physical collimator as electronic collimation
  2. Electronic collimation has improved sensitivity and improved uniformity of the point source response function
  3. For physical collimators, directional info is gained by preventing photons which are not normal or nearly normal to the collimator face from falling on the detector
  4. In electronic collimation, these photons may be detected and used as signal- increased sensitivity
  5. This means typical realisable image resolution in PET is around 5-10 mm compared to SPECT which is 15-20 mm- only v large tumours
  6. Resolution of reconstructed PET images is more uniform than SPECT
  7. PET is superior to SPECT resolution wise and significantly superior to MRI or CT
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14
Q

What is radiolabelling

A
  1. The application of known synthetic methods to target molecules in which at least one atom is present as an isotope other than its naturally most abundant one
  2. Molecules that contain such an isotope are referred to being labelled because such isotopically distinct atoms serve to mark the molecule denoted a marker for later detection
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15
Q

What are the most useful compounds in PET

A
  1. [18F]FDG (Fluorodeoxyglucose)- metabolic imaging
  2. 13NH3 - blood flow
  3. 15O2, H2 15O (H2O)- blood flow
  4. 82Rb-Chloride- myocardial perfusion- accumulates in heart muscle
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16
Q

What is most common radiotracer

A

1.[18F]FDG (18Fluorodeoxyglucose)
2. 95% of all used

17
Q

How is 18

A
  1. H218O + p+ –> 18F- + 2H+ + 1n
  2. 18F- is absorbed on anion exchange column
  3. Add [crypt-2,2,2] + K2CO3 in MeCN to trap 18F
  4. Then added to glucose with OAc groups
  5. THen NaOH, H2O to produce 18FDG
  6. 18F decays to 18O and subsequently glucose emerges as the main reaction product
18
Q

Give advantages of [18F]FDG

A
  1. Convenient diagnostic radiotracer as remains trapped in the tumour
  2. Fluorination means it cannot undergo glycolysis
  3. Can be detected by PET scanner
  4. It can get phosphorylated by hexokinase as normal glucose but cannot be further metabolised so is trapped
19
Q

What are disadvantages of [18F]FDG

A
  1. Only cyclotron availability of 18F and short half life
  2. Only works as a diagnostic in PET for tumours situated in certain locations e.g. lungs
  3. This is due to it being highly hydrophilic so eventually excretes through bladder so abdominal tumours cannot be detected
  4. It crosses BBB in healthy and tumour brains so background contrast cannot be observed - too much glucose in brain
  5. Isn’t specific for hypoxic tumours - late stage diagnosis of large tumours
  6. Also high costs
20
Q

What has both PET and SPECT radionuclides

A
  1. 68Gallium -PET
  2. 67 Ga- SPECT
21
Q

Describe 68Ga and 67Ga

A
  1. Binds as Ga(III) to chelating ligands
  2. t1/2 = 68 mins
  3. PET nuclide obtained from a 68Ge generator which has lifetime of 2 years
  4. 68Ga has 89% decay by positron emission with positron energy of 1.899MeV
22
Q

What are some ligands that are used with Ga

A
  1. Cyclen
  2. DOTA
  3. Variations of DOTA
23
Q

Describe 67Ga

A
  1. SPECT radionuclide produced from cyclotron
  2. 78.27 h half life
24
Q

Describe decay of 68Ga

A
  1. 68,31Ga –> 68,30Zn + 0,1Beta+
  2. Spontaneous decay, gamma rays are generated through recombination of the positron emitted with an electron
25
Q

Why is Ga the isotope of choice for PET

A
  1. Short lived
  2. Used particularly for prostate cancer
  3. Large availability of gallium generators
26
Q

How is 68Ga produced

A
  1. Decay product of 68,32Ge in electron capture decay process
  2. 68,32Ge + e- –> 68,31Ga + v + gamma
  3. Similar action to 99mTc generators
  4. Similar to ion chromatography and using a stationary phase which is either metal-free or alumina, TiO2 or SnO2 onto which 68Ge is adsorbed
  5. Use metal-free columns pre-packaged in these generators allowing direct labelling of Ga-68 without pre-purification, more convenient production than Tc99m.
  6. Mobile phase is a solvent able to elute Ga-68 (III) Typically under acidic pH
27
Q

Once the isotope is eluted from the generator what happens

A
  1. Rapid coordination and stabilisation within a ligand
  2. This often occurs under pH control
  3. If targeted specifically, the entire construct accumulates in a particular part of the body of medical interest
28
Q

What are the two time-critical steps in production

A
  1. Radiochemical synthesis
  2. Quality control and release of the formulated product for injection
29
Q

Describe use of Copper radioisotopes

A
  1. Wide range of radioisotopes with potential uses for SPECT and PET imaging as well as therapy
  2. Can be seen as a true theranostic radionuclide
30
Q

What are the different copper radioistopes and their emissions that are used in medicine

A
  1. 62Cu: beta+, 9.2 min - clean emission but short half life
  2. 64Cu: beta+ and beta-, 12.7 h - low percent emission
  3. 67Cu: beta- and gamma, 62h - clean emission
31
Q

Why is it good to image hypoxia

A
  1. Major pathological process implicated in many disease processes - low Oxygen levels
  2. Major applications of hypoxia imaging:
  3. Oncology: imaging hypoxic tumours
  4. Cardiology: imaging hypoxic/ischaemic myocardium
  5. Hard to treat tumours normally if low O2 levels as activating agent is O
  6. 64Cu in particular used
32
Q

What complex can be used to image hypoxic tumours

A
  1. Bis(Thiosemicarbazone)Cu(II) complex
  2. Effective for PET imaging of hypoxic zone of tumours
  3. R1=R2=Me
  4. With R1=R2=H no hypoxic activity
33
Q

What are the different ligands used

A
  1. PTSM: R1=R3=H, R2=R4=Me
  2. ATSM: R1=R2=R3=Me, R4=H
  3. GTS: R1=R2=R3=R4=H
34
Q

Describe acidity of Cu (I) and (II) and what that means

A

1 Cu(I) is soft lewis acid - Overlaps with S well
2. Cu(II) is medium to hard lewis acid - N are intermediate character
3. So stability for Cu in both oxidation states - Ensures ligands don’t fall apart before delivery of radioisotope

35
Q

What is mechanism of Cu(II)(ATSM)

A
  1. First crosses cell membrane
  2. Then reversible redox reaction to form Cu(I)ATSM-
  3. Also acid controlled Cu(I)ATSM- reacts with 2H+ in reversible reaction to form Cu(I)(ATSMH2)+
  4. Cu(I)ATSM- and Cu(I)(ATSMH2)+ form Cu(I) + ATSMH2
  5. Cu(I) can then enter the metabolism
36
Q

What is [64Cu][Cu(ATSM)] in clinical trials for

A
  1. Tumour hypoxia in head and neck cancers
37
Q

What is problem with

A

aa Radiochemistry (11 decks)

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