Single Photon Emission Computed Tomography (SPECT) Imaging Study to Develop a Biomarker for Alzheimer's Disease

The adaptation of imaging agents like 123-I MNI-388 and 123-I MNI-390 as biomarkers of
β-amyloid deposition in AD patients for assessing disease requires human validation studies.
The purpose of this study is to develop and characterize 123-I MNI-388 and 123-I MNI-390 as
objective biomarkers in AD. The significance of this work lies in applying state-of-art
quantitative neuroimaging tools to develop a relevant biomarker in living AD patients. In
this context we propose to investigate the feasibility of applying this technique as an
imaging biomarker of disease in AD patients.

Informed consent will be obtained for all subjects. All subjects will undergo a screening
evaluation including baseline clinical laboratory testing, a baseline physical and
neurological evaluation and baseline cognitive evaluations. Subjects will be given a bolus
injection of 123-I MNI-388 and MNI 390 in an antecubital vein. Subjects will undergo serial
SPECT imaging scans and serial venous plasma sampling for measurement of 123-I MNI-388 and
MNI 390 in plasma (both protein bound and free) over a period of up to 8 hours. The
quantitative and visual imaging analyses will be performed by an image-processing specialist
who will remain blinded to any clinical information.including diagnosis. The primary imaging
outcome measure will be the brain regional distribution volumes expressed as a brain tissue
to plasma ratio of the radioligand, 123-I MNI-388 and MNI-390. Time to the peak uptake and
amplitude of the peak uptake will be evaluated for all brain regions and the results for the
AD patients and controls will be compared.

Inclusion Criteria:

Alzheimer's Subject Selection: subjects who have a clinical diagnosis of mild to moderate
Alzheimer's disease will be recruited for this study. The following criteria will be met
for inclusion of AD subjects in this study:

- The participant is 50 years or older.

- Written informed consent is obtained.

- Participants have a clinical diagnosis of Alzheimer's disease based on National
Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease
and Related Disorders Association (NINCDS/ADRDA) criteria.

- CDR score ≥0.5 and <2.

- Modified Hachinski Ischemia Scale score of ≤ 4.

- For females, non-child bearing potential or negative urine and blood pregnancy test on
day of 123-I MNI-388 or 123-I MNI-390 injection.

Exclusion Criteria:

Alzheimer's subjects will be excluded from participation for the following reasons:

- The subject has signs or symptoms of another neurodegenerative disease including
Parkinson's disease, diffuse Lewy body dementia, or history of significant
cerebrovascular disease.

- The subject has a clinically significant abnormal laboratory value and/or clinically
significant unstable medical or psychiatric illness

- The subject has any disorder that may interfere with drug absorption distribution,
metabolism, or excretion (including gastrointestinal surgery).

- The subject has evidence of clinically significant gastrointestinal, cardiovascular,
hepatic, renal, hematological, neoplastic, endocrine, neurological, immunodeficiency,
pulmonary, or other disorder or disease.

- Clinically significant MRI evidence of vascular disease or alternative neurologic
disorder

- Pregnancy

Concomitant therapy: patients may remain on a stable dose of anticholinesterase medication
during the study. Use of donepezil (Aricept®), rivastigmine (Exelon®), galantamine
(Razadyne®), tacrine (Cognex®), and memantine (Namenda®) are permitted during the study.
Doses of these compounds must be stable for 2 months prior to the study. At each visit
after the screening visit, the investigator will ask the patient whether any medications
including OTC medications, were taken since the previous visit.

Use of antipsychotics for agitation and benzodiazepines for insomnia or anxiety is
permitted. However, the use of these agents is not permitted within the 8 hours prior to
administration of cognitive testing.

Inclusion Criteria:

Healthy Control Subject Selection: Healthy control subjects who have no neurological
disease will be recruited for this study. The following criteria will be met for inclusion
of healthy control subjects in this study:

- The participant is 50 years or older.

- Written informed consent is obtained.

- Negative history of neurological or psychiatric illness based on evaluation by a
research physician.

- CDR score 0.

- For females, non-child bearing potential or negative urine and blood pregnancy test on
day of 123-I MNI-388 or 123-I MNI-390 injection.

Exclusion Criteria:

Healthy control subjects will be excluded from participation for the following reasons:

- The subject has a clinically significant abnormal laboratory value and/or clinically
significant unstable medical or psychiatric illness.

- The subject has any disorder that may interfere with drug absorption distribution,
metabolism, or excretion (including gastrointestinal surgery).

- The subject has evidence of clinically significant gastrointestinal, cardiovascular,
hepatic, renal, hematological, neoplastic, endocrine, neurological, immunodeficiency,
pulmonary, or other disorder or disease.

- The subject has participated in another clinical study within the previous 30 days.

- Pregnancy

- Clinically significant MRI evidence of vascular disease or neurologic disorder