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aa Radiochemistry > Radioactive substances in medicine 2 -SPECT isotopes > Flashcards

Radioactive substances in medicine 2 -SPECT isotopes Flashcards

1
Q

What is first step in production of 99mTc

A
  1. Start with weapons-grade uranium, highly enriched with 235U
  2. 235,92 U + 1,0 n –> 236,92 U (unstable) –> 99,42 Mo + 134,50 Sn + 3 1,0 n
  3. Yield of 99,42 Mo is tiny via this process
  4. Non-spontaneous fission reaction which occurs through bombardment of accelerated neutrons (e.g. not spontaneous) in cyclotrons
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2
Q

How is 99m Tc formed from 99, 42 Mo

A
  1. 99,42 Mo –> 99m, 43 Tc + 0,-1 Beta- + (v- e)
  2. 99m, 43 Tc –> 99, 43Tc + 0,0 gamma
  3. Gamma radiation is important for imaging
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3
Q

What are alternative pathways to get to 99Mo

A
  1. Other likely fission reactions, followed by beta decay
  2. 235,92U + 1,0n –> 236,92U –>99,40 Zr + 134,52Te +3,0n
  3. 235,92U + 1,0n –> 236,92U + 99,39Y + 134,53I + 3,0n
  4. The 99,40Zr and 99,39Y intermediates formed this way then decay by successive
    beta(-) emissions to 99
    42Mo
  5. Higher yield
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4
Q

Describe transformation of 99,42Mo to 99m,43Tc

A
  1. Mo decays through beta- emission over 90h to 99mTc- spontaneously decays to this excited state
  2. 87% of decays lead to this excited state
  3. Beta- electron and a v antineutrino are emitted in the process
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5
Q

Describe transformation of 99mTc to stable isotope 99Tc

A
  1. Releases gamma radiation which is of medical interest with t1/2 = 6h
  2. 99mTc is an important, metastable, nuclear isomer of 99Tc
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6
Q

Describe decay of 99Tc

A
  1. Decays emitting beta minus particles but no gamma rays
  2. over 200000 years it decays to form stable 99,44Ru
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7
Q

Describe formation of radiopharmaceuticals of 99mTc

A
  1. Takes place in aq medium, therefore affected by:
  2. pH
  3. tin chem of SnCl2
  4. additive used to control O.S of Tc ions
  5. dilution
  6. Os state ranges from +1 to +7 and redox processes are highly pH dependent
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8
Q

What is core of 99mTc radiopharmaceuticals

A
  1. [Tc=O]3+
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9
Q

What is a challenge of 99mTc radiopharmaceuticals

A
  1. Very small concentration of tracer
  2. Under kinetic control
  3. Vast amount of ligand- difficult to handle and control
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10
Q

What are the main applications of 99m Tc radiopharmaceuticals

A
  1. myocardial perfusion imaging for coronary artery disease
  2. A second major application of 99Mo/99mTc generators is whole-body imaging for detection of bone metastases (to a lesser extent for benign bone diseases such as inflammation).
  3. Other applications include sentinel node imaging before surgery for breast cancer or melanoma,
    as well as for thyroid, lung, and renal imaging.
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11
Q

What are limitations of 99mTc radiopharmaceuticals

A
  1. medical radioisotope supply.
    Research scale nuclear reactors (only 6 remaining in the world) means less access to the 99Mo that decays to the 99mTc
  2. Complications in rapid chemistry necessary including access to 99mTc in the differing O.S. needed for the
    radiopharmaceutical of choice, whilst addressing the t1/2 of 6 h in synthetic methodologies.
  3. Kinetics of radiolabelling reactions have to match the first order decay processes of the radioisotope and the relevant t1/2
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12
Q

What are the main practical advantages of 99m-Tc radiopharmaceutical

A
  1. 99mTc can be readily detected in the body by available scanners & medical equipment because it emits ca 140.5 keV gamma rays (these are about the same wavelength as those emitted by conventional X-ray diagnostic equipment),
  2. its half-life for gamma emission is 6 h which is compatible with biological processes;
  3. 94% of it decays to stable, long lived 99Tc in ca 24 hours.
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13
Q

What are 99mTc brain imaging agents used

A
  1. Neurolite (ECD)
  2. Ceretec
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14
Q

Describe properties of 99mTc brain imaging agents

A
  1. Both are neutral compounds
  2. Tc(V) overall with [Tc=O]3+ at the core
  3. Tc is a hard/soft lewis acid so can bind to intermediate lewis base- N and softer lewis base S
  4. Provide high resolution images for diagnosis of trauma
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15
Q

What is a variant of neurolite

A
  1. 99mTc TRODAT
  2. A Tc(V) chelate with [Tc=O]3+ core
  3. Is conjugated to a cocaine derivative specific for dopamine receptors in the brain
  4. Can be used in diagnosis of Parkinson’s disease at an early stage
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16
Q

What are 99mTc heart imaging agents

A
  1. Cardiolite
  2. Myoview
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17
Q

Describe how 99mTc heart imaging agents work

A
  1. Both complexes taken up by myocardial muscle
  2. Substituents chosen to optimise biodistribution, minimise binding to blood plasma proteins, liver uptake, redox characteristics
  3. Give images of diseased heart muscle
18
Q

Describe properties of 99mTc heart imaging agents

A
  1. Both cardiolite and Myoview are +1
  2. Cardiolite is Tc(I) compound
  3. Myoview is Tc(V) compound
19
Q

Describe 99mTc in bone imaging agents

A
  1. Diphosphonate ligands form a range of complexes with TcO4 -
  2. Os is +3 or +4 depending on the pH determined by redox titrations
  3. pH 12-13 = Tc(III)
  4. pH 2-3, 5.4-5.9, 7-7.4 = Tc(IV)
  5. Complexes have free O groups which are used to bind to surface of bone
  6. Can detect bone cancer sites and fractures, expansion to the bone for prostate cancer
  7. Excreted in kidney so also simultaneous indication of their function in cancer patients
20
Q

What are two 99mTc kidney imaging agents used

A
  1. Tc MAG-3
  2. Tc-DMSA
21
Q

Describe properties of kidney imaging agents used

A
  1. MAG-3 provides imporved images with respect to DMSA
  2. Anionic -1
  3. Square pyrimidal geometry
  4. Thiolates assist in reduction of Tc(VII) to Tc(V) inside the ‘kit’ and stabilise the chelate system
  5. Provide images of kidney function
22
Q

Why does Tc bind well to S, O and N

A
  1. Is an intermediate Lewis acid
    in O.S. Tc(III) or Tc(V).
  2. S is a soft lewis base
23
Q

Describe second generation imaging agents

A

1, A stable neutral Tc chelate conjugated to a linker and then targeting group (cyclic peptide) allows targeting of specific areas e.g. binds to receptors expressed in certain forms of breast cancer
2. Peptides control biodistribution of complex in body
3. Tc has large number of OSs which change what it binds to

24
Q

What does a higher oxidation state of Tc mean

A
  1. Binds to harder lewis acids e.g. oxygent
  2. Lower will result in binding to N or S
25
Q

What are 3 important generator-produced radioisotopes for SPECT

A
  1. 99mTc
  2. 188Re, 186Re
  3. I
26
Q

What can Re isotopes be used for

A
  1. Diagnostic and therapeutic
  2. Replace Tc in complexes e,g in Tc-DMSA
27
Q

What is produced in 188,75Re decay reaction

A
  1. Emit electrons and gamma radiation upon spontaneous decay
28
Q

Show decay of 188,75 Re

A
  1. 188,75Re –> 188,76Os + 0,-1b- + 0,0gamma
29
Q

Describe how 188Re is produced and use

A
  1. Generator produced
  2. Analysis involves carrier-free sodium perrhenate by saline elution of the tungsten-188/Re-188 Generator system
  3. Small amount of gamma decay but not well defined so may not be as good at imaging but good in therapy
  4. Can be provided at reasonable costs for routine preparation of radiopharmaceuticals for cancer treatment
30
Q

Describe properties of Re-188 and how this is important for use

A
  1. High energy beta-emitting radioisotope with 16.9 h half life
  2. Beta emission has average energy of 784 keV and a max energy of 2.12 MeV sufficient to penetrate and destroy targeted abnormal properties
  3. Low-abundant gamma emission of 155keV is efficient for imaging and dosimetric calcs
31
Q

What is a limitation of 188Re

A
  1. Rely on availability of fully pharmaceutical grade generators and wide clinical proofs of its interest in radionuclide therapy
32
Q

What is advantage of 188Re

A
  1. Possibility of having a matched theranostic pair with 99mTc
  2. or intrinsically for use as a SPECT/ therapy agent in its own right
33
Q

Give example of 188Re use

A
  1. Analogy with 99mTc(V)-DMSA which is useful for SPECT imaging of medullary carcinoma of thyroid, head, neck tumours and metastasis from breast carcinoma to liver, brain and skeleton)
  2. Thought 188Re(V)-DMSA would be useful for treatment of above cancers.
34
Q

What are the three isomers of 188Re-DMSA that are formed

A
  1. syn-endo-isomer = all COOH groups up in same direction as Re=O bond
  2. Anti-isomer= one side of COOH groups are down and other is up
  3. Syn-exo-isomer= all pointing down
  4. Will see 3 peaks
35
Q

What is limitation of 188Re(V)-DMSA compared to 99mTcDMSA

A
  1. Higher renal accumulation as bigger ion so isn’t excreted as fast
  2. 3 isomers causes problems as not pure so analytical will see 3 peaks- hard to know effects of each
36
Q

What are radioisotopes of I used for

A
  1. In SPECT diagnosis combined with radiotherapy
37
Q

What is general decay scheme for electron capture and what happens in it

A
  1. Z,A X + e- –> Z,A-1 Y + v + gamma
  2. Nucleus of an atom absorbs a K or L shell electron and converts a proton into a neutron
  3. This reduces the atomic number by 1 and emits gamma radiation or an x-ray and a neutrino
38
Q

What is 123I used for and show decay

A
  1. Diagnosis by imaging of variety of cancers e.g. thyroid cancer
  2. 123,53I + 0,-1beta- –> 123,52Te
  3. Decays by electron capture
  4. Half life of 13 h is good for diagnosis
39
Q

What is 131I used for

A
  1. Decays with half-life of 8.02 days (metabolic changes can be monitored) with beta minus and gamma emissions
  2. High energy electrons have good tissue penetration so useful for diagnosis and therapy
  3. 131I is useful in SPECT and therapy particularly for thyroid malfunctions - causes mutation and death in cells that it penetrates due to beta decay
40
Q

Describe decay of 131 I

A
  1. On decaying most often expends 971keV of decay energy by transforming into stable 131Xe
  2. This occurs through an intermediate step
  3. First by beta minus decay, then rapidly followed by gamma decay with production of an antineutrino
41
Q

How can131I be administered

A
  1. As 131I[NaI]
  2. Used for treatment and palliation of thyroid malignancy
42
Q

What is problem with 131I

A
  1. Application in nuclear energy as high energy so medical application is squeezed out

aa Radiochemistry (11 decks)

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