Lecture 4

Question 1

What is preclinical imaging?

Answer 1

The visualisation of living animals for research purposes

Question 2

Why is preclinical imaging useful?

Answer 2

• in drug discovery it acts as an analogous
• it helps us to understand the relation of the biological probe to the desired pathology
• It provides validation keys
• It is hard to model pharmacokinetics and metabolism ex vivo

Question 3

What is preclinical/clinical translation?

Answer 3

From laboratory to first time in man. Translation is successful when preclinical models accurately recapture the clinical situation.

Question 4

What are the four steps of the preclinical protocol?

Answer 4

1. Precursor
2. radio-labelled probe
3. Invitro studies
4. Animal studies

Question 5

The use of animals for research is not taken lightly. What are the three R’s ?

Answer 5

REPLACEMENT- Alternative approaches must be asset
REDUCTION-The number of animals used must be as low as possible
REFINEMENT- continued review of improvement in experimental designs to minimise adverse affects and improve welfare.

Question 6

Describe some parameters that are different between animals and humans that might influence therapeutic response

Answer 6

1. Tumour formation and initiation- large number of cells in mice, clonal from a single cell in humans
2. Site of tumour growth when therapy is initiated- single site in mice ( lung, subcutaneous), multiple sites in humans
3. Genetic background- restricted in mice ( inbreeding), diverse in humans
4. Tumour growth rate- rapid in mice (acute), slow (chronic) in humans
5. Therapy duration- weeks in mice, months in humans

Question 7

Name 6 animal specific factors

Answer 7

1. Anaesthesia- usually by isoflurane
2. Temperature- Mice and rats equilibrate their body temperature to the surface
3. Housing conditions- They affect the physiology of the animals too
4. Fasting state- in metabolism studies this is important
5. Posture- different chambers are provided6. Monitoring- Maintain the physiological status as near to normal as possible

Question 8

Name 5 requirements of a PET detector

Answer 8

1. High detection efficiency
2. High spatial resolution
3. Low dead time
4. Good timing resolution
5. Good energy efficiency