Bridging Study of C11 Pittsburgh Compound B (PiB) and F18 Flutemetamol Brain Positron Emission Tomography (PET)

Study Overview
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Brief Summary
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The intent of this research protocol is to test the equivalency of two amyloid imaging drugs (C11 Pittsburgh Compound B and F18 Flutemetamol). The investigators hypothesize that there will be no significant difference in the distribution of the agents to areas of amyloid deposition in the brain or to other normal brain structures. Recent data have shown similarity in the distribution of the drugs in subjects with Alzheimer's disease (AD) or mild cognitive impairment (MCI). No comparison data of the two PET drugs in normal subjects has been published. It is important to understand differences in the images and biodistribution from the two drugs in normal subjects as nonspecific accumulation of the drugs in brain structures such as white matter appear to differ slightly and could affect image performance.

Detailed Description
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Some of the current thinking in regards to the pathophysiology of AD involves the production of amyloid Beta protein (AB) by secretase processing of amyloid precursor protein (APP). While AB is thought to be toxic to neurons its role leading to AD pathogenesis, this is not without debate. In any case, it appears that AB forms amyloid plaques that are largely ubiquitous in AD. Neuronal cell death as a result of the disease is another clear pathophysiologic finding. Because of the importance of these findings in the development of AD, targeted therapies are being investigated to selectively inhibit AB production and/or manipulate amyloid load. Positron emission tomography (PET) is a molecular imaging modality used to noninvasively measure functional processes of the body. A trace amount of a radiopharmaceutical is injected into a patient and the radiopharmaceutical will be taken up or localized in the body as a function of certain biological processes. The detectors of a PET scanner then measure the radiopharmaceutical distribution externally and the reconstructed PET images should represent the true distribution of the radiopharmaceutical within the body.

Official Title
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Bridging Study of C11 PiB and F18 Flutemetamol Brain PET

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: C11 PiB
* Drug: F18 Flutametamol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females 30 years of age or older. Subjects who have the clinical diagnosis of probable AD (30) ages 50 and older who have a study partner who is the participant's power of attorney (POA) or legally authorized representative (LAR), cognitive normal elderly (30) age >60 and cognitive normal young subjects (30) ages 30-60. Normal subjects with Clinical Dementia Rating (CDR) 0-0.5 and AD subjects with CDR of 0.5 or greater. Exclusion Criteria: Subjects unable to lie down without moving for 30 minutes. Women who are pregnant or who cannot stop breast feeding for 24 hours. Standard safety exclusionary criteria for MRI such as metallic foreign bodies, pacemaker, etc,. Subjects who are too claustrophobic to perform the tests. Subject who have had previous brain irradiation, stroke or brain tumor(s)

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alzheimer's Disease<br>Subjects who have the clinical diagnosis of probable AD ages 50 and older who have a study partner who is the participant's power of attorney (POA) or legally authorized representative (LAR). Interventions include C11 PiB PET/CT and F-18 Flutametamol PET/CT with C11 PiB PET/CT performed first. | Drug: C11 PiB<br>* One time intravenous administration of 8-22 millicurie (mCi) C11 PiB<br>* Other names: C11 Pittsburgh Compound B;Drug: F18 Flutametamol<br>* One time intravenous administration of 3-7 mCi F18 Flutametamol.<br>* Other names: Vizamyl;|
| Active Comparator: Cognitive Normal Elderly<br>Cognitive Normal subjects who are greater than 60 years of age. Interventions include C11 PiB PET/CT and F-18 Flutametamol PET/CT with C11 PiB PET/CT performed first. | Drug: C11 PiB<br>* One time intravenous administration of 8-22 millicurie (mCi) C11 PiB<br>* Other names: C11 Pittsburgh Compound B;Drug: F18 Flutametamol<br>* One time intravenous administration of 3-7 mCi F18 Flutametamol.<br>* Other names: Vizamyl;|
| Active Comparator: Cognitive Normal Young<br>Cognitively normal subjects who are between 30-60 years old. Interventions include C11 PiB PET/CT and F-18 Flutametamol PET/CT with C11 PiB PET/CT performed first. | Drug: C11 PiB<br>* One time intravenous administration of 8-22 millicurie (mCi) C11 PiB<br>* Other names: C11 Pittsburgh Compound B;Drug: F18 Flutametamol<br>* One time intravenous administration of 3-7 mCi F18 Flutametamol.<br>* Other names: Vizamyl;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Distribution of C11 PiB in the Brain | The imaging analysts use a global atlas of the brain to measure the uptake of the radioactive tracer (or brightness) globally. This global uptake was normalized to the uptake in the cerebellar crus region of the brain to get a global Standard Uptake Value Ratio (SUVR). The cerebral crus (crus cerebri) is the anterior portion of the cerebral peduncle which contains the motor tracts. The standard uptake value (SUV) is a way of determining activity in PET imaging. The SUVR is the ratio of SUV from two different regions within the same PET image. For the SUVR, the injected activity, the body weight and the volume to mass conversion factor that are all part of the SUV calculation, cancel. | Approximately one hour after injection of positron emission tomography (PET) drug | 
| Global Distribution of F18 Flutemetamol in the Brain | The imaging analysts use a global atlas of the brain to measure the uptake of the radioactive tracer (or brightness) globally. This global uptake was normalized to the uptake in the cerebellar crus region of the brain to get a global Standard Uptake Value Ratio (SUVR). The cerebral crus (crus cerebri) is the anterior portion of the cerebral peduncle which contains the motor tracts. The standard uptake value (SUV) is a way of determining activity in PET imaging. The SUVR is the ratio of SUV from two different regions within the same PET image. For the SUVR, the injected activity, the body weight and the volume to mass conversion factor that are all part of the SUV calculation, cancel. | Approximately one hour after injection of positron emission tomography (PET) drug |