The purpose of this study is to show that PET-MR imaging can be used for obtaining a pharmacodynamic profile of drugs. By using the 5-HT1B receptor as target we also aim to find effect areas and sizes of the 5-HT1B receptor agonist sumatriptan.
Recent technological advances in multimodal imaging have enabled the simultaneous acquisition of magnetic resonance imaging (MRI) and PET data. Whereas functional MRI (fMRI) provides excellent spatio-temporal resolution for localizing changes in brain activity, PET offers high sensitivity and neurochemical specificity. Together, PET and MRI measures have the potential to help clarify the neurochemical basis of changes in fMRI signal induced by selective exogenous ligands or endogenous neurotransmitter. In the present study we will target the 5-HT1B receptor for which a selective radioligand exist (11C-AZ10419369). The receptor can be stimulated with the agonist sumatriptan, which is used for alleviating migraine attacks. The mechanism of action of sumatriptan is not precisely known and it is unknown to what degree sumatriptan crosses the blood-brain barrier and exerts its effect in the parenchyma. In this study we can determine the blood brain barrier penetration of sumatriptan and thereby evaluate Effect sizes, distribution of signal changes, and correlation between the occupancy at the 5-HT1B receptor in the parenchyma (measured by changes in BPND) and the hemodynamic response (measured by changes in CBF). Ahead of the main study a pilot study will be conducted in which increasing doses of sumatriptan will be tested in the same subject to obtain a dose-response curve. At the same time side effects will be observed and scored. This serves to find the dose with maximum effect size but minimal side effects, which can then be used in the main study for all subjects.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
17
Sumatriptan is a 5-HT1B receptor agonist used for treatment of migraine attacks
Neurobiology Research Unit, Rigshospitalet
Copenhagen, Denmark
Changes in 5-HT1B receptor binding as measured with [11C]AZ10419369
Both measures of receptor binding will be calculated from the same PET-MR acquisition.
Time frame: Two binding potentials are obtained from the 120 min scan: Baseline BPND is determined from 0-50 min. Intervention BPND is determined from 50-120 min.
Changes in cerebral blood flow measured with pseudo continuous Arterial Spin Labeling
CBF will be measured continuous and within the acquisition a dynamic change in CBF upon administration of sumatriptan will be obtained.
Time frame: CBF is measured 15 min prior and 30 min after the injection of sumatriptan giving 45 min of total CBF measurement time.
Change in [11C]AZ10419369 concentration in blood and plasma
Blood samples will be drawn throughout the acquisition time and radioactivity in blood and plasma will be measured.
Time frame: At 2.5, 20, 49, 51, 90 and 120 min after injection of [11C]AZ10419369
Plasma concentration of sumatriptan
Blood samples will taken to measure the plasma concentration of the drug.
Time frame: At -1, 1, 10, 20, 35 and 75 min after injection of sumatriptan
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