Chemistry of technetium

Question 1

Differentiate a radiochemical vs. a radiopharmaceutical

Answer 1

• They are the same
• Radiopharmaceuticals are sterile, pyrogen free, not chemically toxic, and safe for human use
• inherant radiation risk, no pharmacologic effect
• Radiochemicals are not suitable for administration to patients
• not necessary sterile and pyrogen free

Question 2

What are theranostics

Answer 2

• They combine a specific targeted therapy based on a specific targeted diagnostic test
• A key focus on patient care and provides transition fromconventional medicine to more a personalized and precision medicine approach
• Technically old concept but now a large area of focus in NM that continues to grow
• Ex: 131-I, 90-Y, 223-Ra, 177-Lu

Question 3

Unique characteristics of radiopharmaceuticals

Answer 3

• no physiologic effect on the body
• no dose-response relationship
• not chemically toxic; safe for human used
• sterile, non-pyrogenic
• inherant radiation risk: considerations include half-life, critical organ, pathology, energy

Question 4

Describe the ideal radiopharmaceutical

Answer 4

• Short effective half-life
• no particulate emissions
• decay by electron capture or isomeric transition
• high tnt ratio
• suitable energy for imaging
• chemically reactive
• readily available

Question 5

Describe the 2 components of radiopharmaceutical

Answer 5

• Pharmaceutical
• Radionuclide

Question 6

When designing a radiopharmaceutical:

Answer 6

• choose the pharmaceutical first based on its localization in the structure you wish to investigate
• then choose a suitable radionuclide to tag to the radiopharmaceutical

Question 7

Describe the isotopic labelling method

Answer 7

• Radioisotope replaces a stable atom in a compound
• true radiotracers due to the fact: Original biological and structural properties intact
• Routine NM: 131-I, 123-I, 127-I
• PET: 11-C, 13-N, 15-), 18-F
• Ideal approach but there are practical limitatioons
• undersirable radioactive properties for clinical use
• (Unsatisifactory half-life, energy, decay mode

Question 8

Describe the non-isotopic labelling method

Answer 8

• Labeling of molecules not native to compound
• may alter biologic prperties
• Routine RPs: 99m-Tc DTPA, 99m-Tc MDP, 11-In DTPA, and 99m-Tc MIBI
• Two types of non-isotopic labelling method: Technetium tagged and technetium essential

Question 9

Technetium Tagged

Answer 9

• 99m-Tc is a transporting component that delivers it to a specific site in the body
• Biodistribution determined by properties of transporting chemical
  1st generation RPs:
• 99m-Tc MDP: Heterionic exchange
• 99m-Tc SC: Colloid suspension localizes in RES
• 99m-Tc DTPA: metal chelate excreted by GU

Question 10

Technetium essential

Answer 10

• 99m-Tc is the core atom with other components (ligands) arranged around it
• neither ligand or 99m-Tc in the same manner as the 99m-Tc labelled compound
• 99m-Tc added to molecule alters biodistribution
• chelating agent binds radionuclide and biochemical
• 2nd generation RPs
• 99m-Tc IDAs: biliary excretion occurs when 99m-Tc incorperated into molecule
• 99m-Tc MIBI, 99m-Tc HMPAO, 99m-Tc ECD, and 99m-Tc MAG-3

Question 11

Physical Half-Life

Answer 11

• All radionuclides have a unique physical half-life
• this is the time required to reduce its original activity to one half
• 99m-Tc=6hrs
• 131-I=8days
• 68-Ga=78hrs
• 111-In=67hrs

Question 12

Biological half-life

Answer 12

• Radiopharmaceuticals are cleared from the body following an exponential law like radionuclide decay
• Tb is the time required for half of the RP to leavea biological system

Question 13

Effective half-life

Answer 13

• Once a RP is introduced into the human body, both radioactive decay and biological elimination come into play
• The effective half-life is always less than the physical half-life and the biological half-life

Question 14

Redox reactions

Answer 14

• Involve an exchange of electrons between reaching species in a solution
• Results in a change in oxidation state
• degradation of many substances

Question 15

Oxidation

Answer 15

• Increase in oxidation state
• loss of electron or hydrogen, gain of oxygen

Question 16

Reduction

Answer 16

• Decrease in oxidation state
• gain of electrons or hydrogen or a loss of oxygen
• 99m-Tc compound redox reactions often invollve the reduction of TcO4 with stannous chloride

Question 17

Explain Oxidation states

Answer 17

• Transition metals can have multiple oxidation states
• -1 to +7
• Allows incorperation into a variety of chemical forms to be used as RPs
• 0, +2, +6 not useful

Question 18

What are oxidation states influenced by

Answer 18

• pH
• temperature
• Reducing agent
• complexing agent (ligand) most important

Question 19

What is the most stable oxidation state

Answer 19

• 7+: TcO4 (pertechnetate)

Question 20

What will reducing the oxidation state of pertechnetate do?

Answer 20

• pertechnetate will not bind to other chemical species (7+ oxidation state)
• Reducing the oxidation state,usually to 3+,4+, or 5+ makes it more reactive for labelling

Question 21

Why cant SC be reduced?

Answer 21

• Maintains the 7+ oxidation state sue to stability as insolubke technetium heptasufide 99m-Tc2S7
• No reducing agent required

Question 22

Describe the oxidation state of sodium pertechnetate

Answer 22

• Loseselectrons easily and oxidized to 4+ state and then to +7 to form pertechnetate
• +4 and +7 are most stable in aqueous solutions

Question 23

Why doesnt pertechnetate bind effectively to biochemicals

Answer 23

• They can be reduced to a positive charge because its an oxidixing agent (reducing agents added to kits)
• Allows complexing with a variety of ligands/chelates

Question 24

What is the most common reducing agent

Answer 24

• Stannous ion (Sn 2+)
• Powerful reducing agent
• most comon form is stannous chloride (ScCl2)

Question 25

what are other reducing agents

Answer 25

• Ferrous ion
• sodium borohydride
• concentrated HCL
• Electrolysis

Question 26

Ionic bonds in radiopharmacy

Answer 26

• Characterized by the donation of an ellectron
• one atom takes an electron to fill it outer shell and becomes a negative ion; other atom gives an electron and becomes a positive ion
• relatively weak bond
• I.e. Sodium pertechnetate –> pertechnetate ion + sodium

Question 27

Describe covalent bonds in RPs

Answer 27

• Characterized by sharing of a pair of electrons between atoms
• each donates one electron to the bond
• nonpolar covalent bond=electrons may be pulled closer to one atom vs the other
• much stronger than ionic bonds
• Does not dissociate unless is acted upon by a metabolic or chemical process
• I.e. 131-I OIH (hippuran), 99m-Tc MIBI

Question 28

coordinate covalent bonds in RPs

Answer 28

• a pair of electrons aredonated by only one of the atoms
• Partial positive charge is generated on the donor atom and a partial negative charge on the acceptor atom
• I e. H3O
• Some donor atoms have a lone pair of electrons
• these atoms can form coordinate covalent bonds with various metal ion (ie. technetium) to form metal complexes

Question 29

Ligands

Answer 29

• AKA complexing agent, coordinating group
• chemical species that have an unshared pair of electrons that canbe donated to a metal ion to form a complex
• complexes can be cationic, anionic, or neutral
• many radiopharmaceuticals are formed in this manner
• metallic radionuclide + complexing agent (ligand) = Labeled radiopharmaceutical

Question 30

Chelate

Answer 30

• If several sites within the ligand bind to the metal ion
• i.e complexing agent contains multiple donation sites
• forms a ring structure
• The ligand is called a chelating agent
• this mechinism is known as chelation