PET Imaging of Brain Amyloid in Normal Pressure Hydrocephalus

• [18F] Flutemetamol (Drug), also known as Flutemetamol, AH110690: All subjects will receive an intravenous (IV) dose of \[18F\]flutemetamol (less than 10µg flutemetamol). The nominal activity of a single administration of \[18F\]flutemetamol will be 185 megabecquerels (MBq).

Primary outcomes

• Quantitative Estimates of Brain Uptake [18F]Flutemetamol and the Quantitative Immunohistochemical (IHC) Estimates of Amyloid Levels in Biopsy Samples Previously Obtained. [Post-contrast administration]: Radiotracers have enabled the in-vivo imaging of amyloid-beta plaques in the brain, one of the histopathologic hallmarks of Alzheimer's disease (AD). Standardized uptake value ratio SUVR)is the quantitive measure of specific tracer uptake, normalized for the non-specific mean uptake in a reference region. SUVR is calculated as SUV_voi/SUV_ref with SUV being the integrated activity over a given time period for the volume of interest (SUV_voi) or reference region (SUV_ref). VOI means volume of interest and REF means reference region.
• Comparsion Between Brain Uptake of [18F] Flutemetamol Amyloid Level From Immunohistochemistry Assay and a Stained Biopsy Tissue Specimen. [Post-contrast administration]: This was an amyloid level estimate measured by Immunohistochemistry assay to determine the percentage of plaque area for mAb NAB228. The Immuno-histo chemical reagent was monoclonal antibody (mAB) NAB228. This is a percentage of the area of the biopsy tissue specimen that stains positive for amyloid using NAB228.

Secondary outcomes

• Quantitative Estimates of Amyloid Levels ( Percent % Plaque Load) for the Following 7 Subjects [Post-contrast Administration]: Using the Precent area of Plaque values from the Primary Anaylsis, determine the association between cerebral cortical uptake of \[18F\] flutemetamol (as contralateral, ipsilateral, and composite SUVR values) and Immunohistochemical and histochemical-based estimates of amyloid.

Sex: All, ages: 50 Years to any

Inclusion Criteria:

* The subject is 50 years old or older.
* The subject has had a frontal lobe cortical biopsy adequate for the detection and quantitation of amyloid.
* Informed consent has been signed and dated by the subject/and/or subjects' legally acceptable representative, if applicable, in accordance with local regulations.

Exclusion Criteria:

* The subject has a contraindication for MRI or PET.
* The subject has a known or suspected hypersensitivity/allergy to \[18F\]flutemetamol.
* The subject has participated in any clinical study using an investigational agent within 30 days of dosing.

Participant flow

Outcome results

• Quantitative Estimates of Brain Uptake [18F]Flutemetamol and the Quantitative Immunohistochemical (IHC) Estimates of Amyloid Levels in Biopsy Samples Previously Obtained. (Primary), Number, Standard Uptake Value Ratio (SUVR): Subject 201-0001 1.59; Subject 201-0002 1.56; Subject 201-0003 1.25; Subject 201-0004 2.17; Subject 201-0005 2.07; Subject 201-0006 1.39; Subject 201-0007 1.00
• Comparsion Between Brain Uptake of [18F] Flutemetamol Amyloid Level From Immunohistochemistry Assay and a Stained Biopsy Tissue Specimen. (Primary), Number, Percent plaque area: Subject 201-0001 0.127; Subject 201-0002 0.447; Subject 201-0003 0; Subject 201-0004 1.007; Subject 201-0005 0.4; Subject 201-0006 0; Subject 201-0007 0
• Quantitative Estimates of Amyloid Levels ( Percent % Plaque Load) for the Following 7 Subjects (Secondary), Number, Percentage of Plaque: Amyloid Level (Plaque Load) 0.127 (p 0.098)

Adverse events

Other adverse events by term

• Kim A Mansfield, MS, Study director, GE Healthcare