Novel Positron Emission Tomography (PET) Radiotracer to Image Phosphodiesterase-4B (PDE4B)
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|ClinicalTrials.gov Identifier: NCT03030391|
Recruitment Status : Terminated
First Posted : January 25, 2017
Last Update Posted : December 17, 2019
The new drug 18F-PF-06445974 has a little radioactivity. This can be seen by a positron emission tomography (PET) scan. The drug helps researchers see a protein, PDE4B, in the brain. Looking at PDE4B in the living brain might show how it is involved in psychiatric and neurological disorders. One part of the study will look at how the study drug is distributed in the brain. Another part will study how brain measures vary.
To measure the protein PDE4B in the brain. To test how a new radioactive chemical, 18F-PF-06445974, is distributed in the body.
Healthy adults ages 18 and older
Participants will have 1-3 visits over a year. Each will be 2-5 hours.
Women will have a pregnancy test each time.
|Condition or disease||Intervention/treatment||Phase|
|Healthy||Other: PET Other: MRI||Phase 1|
Phosphodiesterase type 4 (PDE4) terminates signal transduction of guanine nucleotidebinding proteins (G-protein)-coupled receptors by metabolizing the second messenger 3 <=,5 <=- cyclic adenosine monophosphate (cAMP). PDE4 is selective to cAMP over cyclic guanosine monophosphate. PDE4 has four isozymes A, B, C, and D and basic studies indicate that type B (PDE4B) plays a key role in cognitive function and neuroinflammation. Thus, PDE4B inhibitors would be expected to improve cognitive function and have anti-inflammatory effects. Pfizer has developed a new PET ligand, 18F-PF-06445974, to selectively image PDE4B; the ligand has shown promising results in non-human primates.
This protocol covers four phases:
- Phase 1: whole body imaging of one subject with a low injection activity of 2 mCi to confirm that no organ has prominently high uptake of 18F-PF-06445974;
- Phase 2: kinetic brain imaging with up to 5 mCi injection to quantify PDE4B in brain relative to concurrent measurement of the parent radioligand in arterial plasma;
- Phase 3: if 18F-PF-06445974 is successful in Phase 2 in the first couple of subjects, we will estimate the radiation-absorbed doses by performing whole body imaging with 5 mCi injection;
- Phase 4: test-retest analysis of brain binding relative to concurrent measurement of the parent radioligand in arterial plasma (5 mCi per scan).
Healthy adult female and male volunteers (n=22, ages 18 or older) will undergo brain imaging. An additional eight healthy volunteers will undergo whole body dosimetry analysis, for a total of 30 healthy volunteers.
For quantification of 18F-PF-06445974, 22 healthy controls will undergo brain PET imaging using 18F-PF-06445974 and an arterial line. Some of them will have a test-retest scan. Eight additional subjects will have a whole body PET scan for dosimetry. For dosimetry, no arterial line will be used.
To assess quantitation of PDE4B with 18F-PF-06445974, we will primarily use two outcome measures, namely the identifiability and time stability of distribution volume (VT) calculated with compartmental modeling. In the test-retest study, we will calculate the retest
variability. We will assess whole-body biodistribution and dosimetry of 18F-PF-06445974 by calculating doses to organs and effective dose to the body.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||5 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Evaluation of a Novel Positron Emission Tomography (PET) Radiotracer to Image Phosphodiesterase-4B (PDE4B)|
|Study Start Date :||January 10, 2017|
|Actual Primary Completion Date :||March 16, 2018|
|Actual Study Completion Date :||March 16, 2018|
- Quantification of 18F-PF-06445974 binding in brain [ Time Frame: 2 hours ]
- Biodistribution of 18F-PF-06445974 in the body. [ Time Frame: 2 hours ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03030391
|United States, Maryland|
|National Institutes of Health Clinical Center|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Masahiro Fujita, M.D.||National Institute of Mental Health (NIMH)|