1. Goal:

2. design

3. 11C-FLB457 perospirone Why?

4. In the Arakawa paper, where does the baseline (aka ‘control’) data come from? From Vernaleken et al…

5. DOES THIS MAKE SENSE?

6. Design of healthy control study: This is a “single dose” study – why? As opposed to _______________?

7. Design of healthy control study: 11C-raclopride Baseline 11C-raclopride perospirone This is a “single dose” study – why? As opposed to _______________?

8. Healthy controls Why use 11C-raclopride here?

9. Goal:

10. design ‘short’ ‘long’

11. design Ziprasodone ‘short’ ‘long’ 11C-fallypride

12. Again, where do the baseline data come from in this design? Can they do that? Problems?

13. Allows for different levels of occupancy for different regions. Multiple doses of drug, I guess

14. Lower EC 50 for putamen compared to other (extrastriatal) regions means lower receptor occupancy by the drug (ziprasodone) for a given plasma concentration.

15. Suggests that there is a discrepancy between single dose measurements of occupancy and ‘steady state dosing’ But what else could it be? Perhaps: Chronic treatment with Zipras leads to upregulation of receptors and lower occup levels…

16. 001

17. Healthy controls Why use 11C-raclopride here? Dosimetry? Repeated scans on same day? Displaceability in striatum? DIFFERENT STUDIES DONE AT DIFFERENT CENTERS

18. Goal:

23. But to do microdose study, the drug company would have to give the chemical formula to the university PET center… so they could label it.