Part 2: L6, Theranostics and Bimodal

Question 1

What is bimodal imaging?

Answer 1

• Single probe that can be detected by two different imaging methods (modalities)
• Same agent thus confidence that localisation is identical
• Lower dose of potentially toxic chemicals in patient

Question 2

For each modality, list traditional agents, tissue penetration and resolution:

Answer 2

• CT: None/heavy atom, deep, micrometers
• MRI: Gd3+, Dy3+, Mn2+, Deep, millimeters
• PET: Radioisotopes, deep, mm
• SPECT: Radioisotopes, deep, mm
• Fluorescence Microscopy: Fluorochromes, rhodamines, BODIPYs etc, shallow, 100s of nm

Question 3

3 key options for bimodal imaging:

Answer 3

• Radio + MRI (limited usefulness)
• Radio + fluor.
• MRI + fluor.

Question 4

Pros and cons of combining MRI and fluorescence:

Answer 4

• Complementary scales (both whole body and subcellular covered between the two)
• Issue: Mismatch in doses (micrograms vs 10s of gs)
• Also, paramagnetism often quenches fluorescence

Question 5

Pros and cons of combining MRI and Radio:

Answer 5

• MRI can report on environment and complement PET
• Issue: not much difference in penetration / resolution
• Doses very mismatched (worse than MRI + fluor)

Question 6

Pros and cons of combining radio and fluorescence:

Answer 6

• Complementary scales (resolution etc, whole body and subcellular)
• No interference between signals
• Both detected by optics
• However, the doses are mismatched, and some PET complexes are paramagnetic (quenching)

Question 7

Why is agent degradation an issue in bimodal imaging? What is a design principle to avoid this?

Answer 7

• If each modality is operating through a distinct part of the agent, separation is a real risk
• Agents can separate and thus localise differently
• Can produce a false negative for e.g. fluorescent sensing
• Use of single core sructures (SCoMPI) -> if the same unit responsible for fluorescence and radio (i.e. radioisotope and fluorescent) cannot be separated

Question 8

Describe theranostics:

Answer 8

• Combining therapy and diagnosis
• Covers many modes of therapy and many modes of imaging -> course focusses on PDT with fluorescence

Question 9

What is PDT?

Answer 9

• Photodynamic therapy
• Fluorescent agents to be used as photosensitizers (toxic when irradiated)
• Phototherapeutic Index: Ratio of toxicity in light versus dark

Question 10

Mechanism of photosensitization:

Answer 10

• Generation of singlet oxygen from reaction of triplet oxygen ground state with tripled excited state of fluorophore