Angelo Amoroso

Question 1

Four Synthetic Protocols to synthesis SPIONs

Answer 1

• Co-precipitation
• Constrained Environment
• Hydrothermal High temp
• Sonolysis

Question 2

Why are SPIONs typically coated?

Answer 2

• Stabilisation, prevents particles from aggregation in biological conditions. In iron oxide the surface iron acts as a Lewis acid and co-ordinates ligands. The replacement of surface OH groups is pH dependent.
• Functionality, add groups for different biological applications

Question 3

How can SPIONs be functionalised to allow conjugation?

Answer 3

Coat the nanoparticles with silica. An R group on the Silica can contain a functional group (e.g NH2) from which we can link to the surface.

Question 4

Positive Contrast Imaging

Answer 4

A positive contrast agent is a species that causes a significant change in the T1 relaxation time

Question 5

Negative contrast Imaging

Answer 5

A negative contrast agent is a species that causes a significant change in the T2 relaxation time

Question 6

Example of a positive and negative contrast agent.

With both species indicate what makes them good contrast agents

Answer 6

Positive - Gd(III) comple - Gd-DOTA

• High spin F7 configuration
• Large magnetic moment
• Symmetrical spin states
• electron relaxation (Gd) needs to be a similar relaxation to the nuclei

Negative - SPIONs - Fe3O4

• Highly paramagnetic material
• disturb the field homogeneity causing rapid dephasing of the bulk

Question 7

How do water exchange rates affect r1 relaxivity?

Answer 7

• exchange rate is 1/lifetime in inner sphere
• The exchange rate is proportional to relaxivity so increase the exchange rate increase r1 (more water molecules relaxed)
• However there if the exchange rate is too high then r1 can start to decrease (Not enough time spent on complex to relax)

Question 8

Explain why increase in relaxivity is expected but often not observed?

Answer 8

• Generally as we increase the size of the molecule (MWt), the tumbling decreases, which increases relaxivity.
• However this is not always observed as tumbling is dependent on internal flexibility (dependent on segmental motion)

Question 9

Features that must be present for in-vivo application

Answer 9

• Non toxic
• Functional contrast agent
• Significant change in T1 and T2 values

Question 10

Name MRI stimulus’ in biological environments

Answer 10

• pH responsive

- Enzyme responsive

Question 11

Name MRI stimulus’ in biological environments and how they could function

Answer 11

pH responsive

• A change in pH could increase tumbling time as molecules could shrink (long chain polymers)
• A change in pH could alter q (displace water)

Enzyme responsive
-In the presence of an enzyme, make space for water molecules to coordinate (chopping of moiety). Change q

Question 12

Key parameters that affect relaxivity

Answer 12

• q number
• optimising water exchange rates
• tumbling rate

Question 13

How do sterics effect water exchange?

Answer 13

• Only affected by sterics of the inner sphere!
• Replacing carboxylate for an amide decrease exchange rate by 3-4 times
• The carboxylate is more crowded i.e the coordination of the O- is shorter and favours dissociation of water (water squeezed out)

Question 14

How do Charge effect water exchange?

Answer 14

A higher negative charge favours the leaving of the water molecule

Question 15

How does the number of water molecules affect water exchange?

Answer 15

More water molecules = less stereo-rigidity

therefore increasing water exchange

Question 16

Alternative the Gd(III) complexes

Answer 16

Mn(II)
Relaxivity is poorer but less toxic
Can trap in liposomes to decrease toxicity and have high relaxivity

Question 17

Describe a pulse sequence that will result in a T1-weighted image.

Answer 17

Draw a pulse sequence showing TR, TE, 90degree pulse, 180degree pulse and spin echo.
For a T1 weighted image you would need a short TR time and a short TE time. This will maximise contrast for T1.
short TE negates any differences in T2.

Question 18

The required TR & TE for a T1 weighted exp, T2 weighted exp and proton density contrast

Answer 18

-T1 weighted exp:
TR short TE short
-T2 weighted exp:
TR long TE long
-Proton Density
TR long TE short

Question 19

Sequence for a proton weighted image?

Answer 19

• Allow all protons to count the same, allow all to relax back up (long TR)
• No significant difference in de-phasing (short TE)
• Every proton is the same, can integrate for proton density

Question 20

Co-precipitaion

Answer 20

• Simplest method
• Size and shape may be tailored by adjusting pH, ionic strength, temperature, counter-ion, rate of addition, rate of stirring.
• Wide range of particle diameter
• Add citrate to control diameter to 3nm (coating of citrate inhibits growth)

Question 21

Constrained environment

Answer 21

-Use of surfactants to create water swollen reverse micellular structures in non-polar solvents in which NP can form

Question 22

Hydrothermal/High Temp

Answer 22

Nanoparticles with a high level of mono-disperity and size control can be prepared by the high temperature decomposition of iron organic precursors. (Fe(CO)5 or Fe(acac)3)

Question 23

Sonolysis

Answer 23

shape and size of the nanoparticles can be adjusted by varying the operating parameters which
include ultrasonic power, current density, deposition potential and the ultrasonic vs
electrochemical pulse times.

Question 24

r(obs) equation ?

Answer 24

r(obs) = 1/T(dia) + (r(i) x [Gd])

r(i) = 1/T1