Florbetapir Calibration to the Centiloid Scale

Phase 1

Completed

Brief Summary: This study is designed to demonstrate the conversion of florbetapir (18F) Positron Emission Tomography (PET) Standard Uptake Value ratio (SUVr) to Centiloid units.

Recruitment & Eligibility

Inclusion Criteria

Cognitively Normal Subjects
- Males or females ≥ 21 and ≤ 45 years of age
- Mini-mental state examination (MMSE) ≥ 29
Clinically Diagnosed AD Subject
- Males or females ≥ 50 years of age
- Meet clinical criteria for dementia due to probable AD
- MMSE ≥ 16 and ≤ 26
Possible AD Subject
- Males or females ≥ 50 years of age
- Meet clinical criteria for dementia due to possible AD
- MMSE ≥ 16 and ≤ 26
MCI Subject
- Males or females ≥ 60 years of age with cognitive impairment (not dementia)
- MMSE >24 and <29
At Risk Elderly Subject
- Cognitively normal males or females that are known ApoE4 carriers and ≥ 75 years of age
- MMSE ≥ 27

Exclusion Criteria

Have had or currently have a diagnosis of neurodegenerative disorders other than AD
Have a current serious or unstable illness that could interfere with completion of the study
Subject has a known brain lesion, pathology or traumatic brain injury
Have received or participated in a trial with investigational medications in the past 30 days
Have had a radiopharmaceutical imaging or treatment procedure within 7 days of study imaging session
Females of childbearing potential who are not surgically sterile, not refraining from sexual activity or not using reliable methods of contraception

Arm && Interventions

Group	Intervention	Description
Amyloid Positive Subjects	11C-PiB	Approximately 25 subjects with a range of amyloid density comprised of subjects clinically diagnosed with Alzheimer's Disease (AD) and subjects at risk for elevated amyloid density will receive a single i.v. bolus injection of approximately 370 MBq (10 mCi) florbetapir (18F) and a single i.v. bolus injection of approximately 555 MBq (15 mCi) 11C-PiB.
Amyloid Negative Subjects	11C-PiB	Approximately 10 cognitively normal young subjects will receive a single i.v. bolus injection of approximately 370 megabecquerel (MBq) (10 millicurie \[mCi\]) florbetapir (18F) and a single i.v. bolus injection of approximately 555 MBq (15 mCi) 11C-PiB.
Amyloid Negative Subjects	Florbetapir (18F)	Approximately 10 cognitively normal young subjects will receive a single i.v. bolus injection of approximately 370 megabecquerel (MBq) (10 millicurie \[mCi\]) florbetapir (18F) and a single i.v. bolus injection of approximately 555 MBq (15 mCi) 11C-PiB.
Amyloid Positive Subjects	Florbetapir (18F)	Approximately 25 subjects with a range of amyloid density comprised of subjects clinically diagnosed with Alzheimer's Disease (AD) and subjects at risk for elevated amyloid density will receive a single i.v. bolus injection of approximately 370 MBq (10 mCi) florbetapir (18F) and a single i.v. bolus injection of approximately 555 MBq (15 mCi) 11C-PiB.

Primary Outcome Measures

Name	Time	Method
Florbetapir SUVr Conversion to Centiloid Units	up to 70 minutes post injection	Conversion of florbetapir (18F) positron emission tomography (PET) standard uptake value ratio (SUVr) to Centiloid units. The Centiloid is anchored at values of 0 and 100 corresponding to the median Pittsburgh Compound B (11C-PiB) SUVr value for a representative group of young (\<45) cognitively and medically healthy control subjects (YHC) and the median SUVr value for a representative group of 11C-PiB positive patients diagnosed with Alzheimer's disease, respectively. A cortical average to cerebellum SUVr was used for this outcome measure.

Secondary Outcome Measures

Name	Time	Method
Correlation of Florbetapir (18F) Centiloid and 11C-PiB Centiloid	up to 70 minutes post injection	Correlation coefficient between 11C-PiB and florbetapir (18F) SUVr as converted to centiloid units. The Centiloid is anchored at values of 0 and 100 corresponding to the median Pittsburgh Compound B (11C-PiB) SUVr value for a representative group of young (\<45) cognitively and medically healthy control subjects (YHC) and the median SUVr value for a representative group of 11C-PiB positive patients diagnosed with Alzheimer's disease, respectively. A cortical average to cerebellum SUVr was used for this outcome measure.
Variability of PET Images in Young Healthy Control Subjects.	up to 70 minutes post injection	Coefficient of variation for 11C-PiB and florbetapir (18F) SUVr. A cortical average to cerebellum SUVr was used for this outcome measure.