Transcript Lecture12-drug-occupancy-studies

Goal:
design
design
perospirone
11C-FLB457
perospirone
11C-FLB457
perospirone
11C-FLB457
perospirone
perospirone
perospirone
Why?
11C-FLB457
11C-FLB457
11C-FLB457
From Vernaleken et al…
In the Arakawa paper, where does the baseline
(aka ‘control’) data come from?
From Vernaleken et al…
DOES THIS MAKE SENSE?
Design of healthy control study:
This is a “single dose” study – why?
As opposed to _______________?
Design of healthy control study:
11C-raclopride
Baseline
perospirone
11C-raclopride
11C-raclopride
This is a “single dose” study – why?
As opposed to _______________?
11C-raclopride
Healthy controls
Why use 11C-raclopride here?
Goal:
design
‘short’
‘long’
design
‘short’
Ziprasodone
Ziprasodone
Ziprasodone
Ziprasodone
Ziprasodone
Ziprasodone
‘long’
11C-fallypride
11C-fallypride
11C-fallypride
11C-fallypride
11C-fallypride
11C-fallypride
Again, where do the baseline data come from in this
design?
Can they do that? Problems?
Allows for different levels
of occupancy for different
regions.
Multiple doses of
drug, I guess
Lower EC50 for putamen compared to other (extrastriatal) regions
means lower receptor occupancy by the drug (ziprasodone) for a
given plasma concentration.
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…
001
Healthy controls
Why use 11C-raclopride here?
Dosimetry?
Repeated scans on same day?
Displaceability in striatum?
DIFFERENT STUDIES DONE AT DIFFERENT
CENTERS
Goal:
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.