Evaluation of [18F] FEPPA and PET Imaging as a Marker of Inflammation in Subjects With Neurological Conditions

The adaptation of imaging agents like [18F]-FEPPA as a biomarker of microglial activation in neurodegenerative and neuroinflammatory diseases requires human validation studies. Expanding upon our previous work with B-amyloid ligands (123I-IMPY, 123I MNI-187) for AD and dopamine transporter ligands (123I B-CIT, Altropane) for PD, we desire to develop and characterize [18F]-FEPPA as a potential marker for microglial activation in association with neuronal damage that may be applicable to multiple neurodegenerative and inflammatory diseases.

Inclusion criteria

• Alzheimer's disease patients 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 probable Alzheimer's disease based on National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria.
• Clinical Dementia Rating Scale score ≤ 2.
• Modified Hachinski Ischemia Scale score of ≤ 4.
• For females, non-child bearing potential or a negative urine or blood pregnancy test on day of [18F]-FEPPA injection.

Exclusion criteria

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

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

Inclusion criteria

• The following criteria will be met for inclusion of PD subjects in this study:

• The participant is 30 years or older.
• Written informed consent is obtained.
• Participants have a clinical diagnosis of Parkinson disease (at least two of the three cardinal symptoms: resting tremor, rigidity, bradykinesia).
• Hoehn and Yahr ≤4.
• For females, non-child bearing potential or a negative urine or blood pregnancy test on day of [18F]-FEPPA injection.

Exclusion criteria

• Parkinson's 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 evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, neurological, immunodeficiency, pulmonary, or other disorder or disease.
• Pregnancy

Inclusion criteria

• Multiple Sclerosis Subject Selection. Subjects who have a clinical diagnosis of Multiple Sclerosis (MS) will be recruited for this study. The following criteria will be met for inclusion of MS subjects in this study:

• The participant is 18 years or older.
• Written informed consent is obtained.
• Participants have a clinical diagnosis of Multiple Sclerosis (per the 2005 Revised McDonald Criteria; Polman, et al., 2005).
• Kurtzke Expanded Disability Status Scale (EDSS) ≤ 7.5.
• For females, non-child bearing potential or a negative urine or blood pregnancy test on day of [18F]-FEPPA injection.

Exclusion criteria

• MS 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 evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, neurological, immunodeficiency, pulmonary, or other disorder or disease.
• Pregnancy