Part 1: L6 Gamma Camera/SPECT

Question 1

Overview of radiochemistry for SPECT:

Answer 1

• e.g. Parent nucleus of U-238 emits alpha particles -> excited daughter particles which emits gamma ray
• Alt: Beta and gamma decay modes - positron from unstable artificial isotopes
• SPECT requires gamma particles

Question 2

Radionuclides:

Answer 2

• Primarily showing physiological function -> localising
• Gamma-emitting radioisotopes which passes through tissue without being scattered, or causing much damage
• Can enter cells
• Generally administered in very low doses (ng)

Question 3

SPECT technology:

Answer 3

• Single photon emission computed tomography
• Gamma camera
• Radioactive event releases gamma particles -> collumate with lead fingers -> only photons directly upwards allowed -> Aluminium casing then scintillation crystal, photomultiply -> detect and trasnmit information to computer
• Collimator is also one of the sources of blurring within the image, attenuates most (>99%) of incident photons
• This limits the sensitivity

Question 4

Nucleotide Limitations in SPECT:

Answer 4

• Most gamma cameras are designed for specific energy windows (100-250 eV)
• Lower than this: too scattered
• Higher than this: difficult to collimate
• Half-life must be long enough to synthesis and allow accumulation in target tissue, while allowing clearance through non-target organs -> short as possible to limit radiation dose
• Desired half life is dependent on time required to localise to target tissue (heart/brain: shorter, tumour targeted radiolabelled monoclonal antibodies take longer)

Question 5

Typical sourcing of radionuclides:

Answer 5

• Generators considered ideal, preferably with low cost parent isotopes
• Daughter can be easily separated from the parent via either ion exchange chromatography or solvent extraction
• A few isotopes are produced in a nuclear reactor
• Several can be generated by an accelerator or cyclotron - expensive - and can only produce one isotope at a time

Question 6

Tc-99m qualities:

Answer 6

• 6hr half-life
• Generated in 99Mo/99mTc generator
• Decays via isomeric transition

Question 7

How are radionuclides administered?

Answer 7

• Intravenous injection in liquid or aggregate form (majority)
• Ingestion while combined with food
• Inhalation as a gas or aerosol (Xenon-133m/Krypton-81m)
• Some studies require the labelling of a patient’s own blood cells with a radionuclide leukocyte and red blood scintigraphy

Question 8

Iodine-123 in SPECT

Answer 8

• Half life of 13.13 hrs
• Decays via gamma particle
• Can be used for things like thyroid

Question 9

Xenon-133m in SPECT:

Answer 9

• Inhaled to assess pulmonary function and to image lungs
• Also often used to image blood flow
• Rapid clearance from brain

Question 10

Technecium-99m in SPECT:

Answer 10

• Most prevalent agent (85% of administered drugs)
• Can be gaseous
• Emits a 140 keV gamma-ray with 89% abundance and a 6hr half life
• There is no stable isotope (middle of transition metals)
• Versatile and simple chemistry (t.metal)
• Made in 99Mo/99mTc generator

Question 11

Thallium-201 in SPECT:

Answer 11

• Historically used to image heart
• Very toxic -> alopecia
• Cyclotron produced
• Half life 72.5hrs
• TI decays emitting Hg X-rays and photons
• Behaves similarly to potassium in body (Tl(I)) -> taken up well via sodium/potassium pump -> collects in myocardium then circulated out rapidly
• Able to image heart in real time -> Thallium stress test
• Has since been replaced by Sestimibi (Tc-99m based)

Question 12

99m-Tc generation:

Answer 12

• Molybdate (2- anion) decays to Pertechnetate in luminar column; single negative charge as Tc so able to wash off with 0.9% NaCl
• Obtained in evac vial with lead shielding
• Charge chromatography where Mo binds strongly and Tc elutes

Question 13

Tc essential:

Answer 13

• First class of 99mTc pharmaceuticals
• Tc is an essential structural part of the introduced drug
• Majority

Question 14

Tct-tagged

Answer 14

• Minority
• The physiologically active targeting moiety such as an antibody, peptide, hormone etc has been labelled with 99mTc by a bifunctional chelate

Question 15

Brain imaging with Technecium-99m

Answer 15

• Kits are available for the radiographer with essential components for ‘one pot’ solution
• Ceretec, neurolite etc -> Tc5+ formed by reduction with SnCl2, followed by complexation with the ligand in a saline solution
• Capable of penetrating the intact BBB due to their neutral and lipophilic character

Question 16

Tc SPECT agents in myocardial imaging;

Answer 16

• Myoview (note lipophilic chains)
• -> Kit of tetrafosmin (ligands), SnCl2, disodium, sulfosalicylate (balance acidity), sodium D-g, sodium hydrogen carbonate
• Cardiolite (note pi-acceptor ligands) -> tumour uptake

Question 17

Research application of Tc agents:

Answer 17

• Research into localisation of drugs
• Assessing which are the active parts of drugs
• Clinical trials