Objective:

In response to brain inflammation, microglia over-express the peripheral benzodiazepine receptor (PBR). Although peripheral organs such as the heart and kidney express PBR constitutively, the brain normally expresses PBR in low numbers. Increased PBR density in the brain therefore signifies a change from a normal state to an active, inflammatory state. Positron emission tomography (PET) imaging can quantify PBR density in vivo using radioligands that bind to PBR sites. One PBR-selective radioligand, [11C](R)-PK 11195, has been used to identify areas of brain inflammation in patients with various neurological diseases. Unfortunately, [11C](R)-PK 11195 has several limitations, including low specific signal. A recently developed radioligand, [11C]PBR28, has higher specificity than [11C](R)-PK 11195 for PBR in animal studies. No study to date has compared [11C]PBR28 to [11C](R)-PK 11195 in human subjects.

In early clinical studies using [11C]PBR28, 4 of 32 healthy human subjects had complete absence of radioligand binding, even in peripheral organs that constitutively express PBR. One of these non-binders had specific binding of PBR28 on an in vitro assay using peripheral lymphocytes. We do not know why some subjects have [11C]PBR28 binding while others do not. We also do not know why one non-binder had positive in vitro binding and negative in vivo binding on PET imaging. No study has reported absent binding with [11C](R)-PK 11195. In order to better understand the phenomenon of non-binding, we need to obtain [11C](R)-PK 11195 PET scans in subjects that are [11C]PBR28 non-binders.

Study Population:

This protocol will study a total of 30 healthy human volunteers.

Design:

Fifteen subjects will undergo PET imaging with [11C]PBR28 and [11C](R)-PK 11195 using arterial blood sampling for fully quantitative image analysis. These subjects may have dedicated brain PET imaging or whole body PET imaging.

Fifteen subjects will undergo PET imaging with [11C]PBR28 and [11C](R)-PK 11195 without arterial blood sampling. These subjects will have whole body PET imaging.

All subjects will have in vitro PBR28 binding assays performed.

Outcome Measures:

Our primary outcome measures will be the distribution volume and time stability of each radioligand. We also wish to determine if subjects with absent [11C]PBR28 binding also have absent [11C](R)-PK 11195 binding. The presence or absence of [11C]PBR28 and [11C](R)-PK 11195 binding will be evaluated in brain and in peripheral organs. Lastly, we will measure in vitro binding of PBR28 by performing binding assays using peripheral blood cells.