PET Imaging of Peripheral Benzodiazepine Receptors in Patients With Neurocysticercosis Using [F-18]FB

Objective

In endemic regions neurocysticercosis is the most common cause of adult acquired epilepsy and
thus an important public health problem. The disease is caused by infection with the larval
form of the tapeworm, Taenia solium. Although neurocysticercosis is common only in many
developing regions, an increased number of patients are diagnosed in developed countries
mostly due to immigration of infected individuals.

The peripheral benzodiazepine receptor (PBR) can be a clinically useful marker to detect
neuroinflammation because activated microglia in inflammatory areas expresses high levels of
PBR. PBR has been imaged with positron emission tomography (PET) using [(11)
C]1-(2-chlorophenyl-N-methylpropyl)-3-isoquinoline carboxamide (PK11195), which provides low
levels of specific signal. Recently we developed a new ligand,
N-fluroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline ([(18)F]FBR), which showed much
greater specific signals than [(11) C]PK11195 in non-human primates.

The major objective of this protocol is to assess the utility of [(18) F]FBR PET to detect
neuroinflammation in patients with neurocysticercosis.

A secondary objective is to study whether some healthy subjects do not show binding of
[(18)F]FBR by performing whole body imaging using [18F]FBR and binding assays using blood
cells. In other protocols using a PET ligand with similar structure, [(11)C]PBR28,
approximately 8% of subjects (9/~ 118 ) did not show binding. In protocols 07-N-0035 and
08-M-0158, we compared binding of [11C]PBR28 and [(11)C]PK 11195 in approximately ten healthy
subjects including five who did not show binding of [(11)C]PBR28 in prior whole body imaging.
We found differences in organs with regard to sensitivity to the phenomenon of non-binding.
In the non-binders, PBR28 showed no binding in all five organs with high PBR density.
However, PK 11195 showed significantly reduced binding in only two organs with PBR. We now
wish to determine whether PBR06 is more similar to PBR28 or to PK 11195 in terms of the
non-binding phenomenon. In the current protocol, in addition to whole body imaging using
[(18)F]FBR, we will do in vitro binding assays using blood cells as another tissue to examine
the effect of non-binding.

Study population

For [(18)F]FBR brain scans, ten patients will be recruited and clinically followed under
protocol 85-I-0127, Treatment of Cysticercosis including Neurocysticercosis with Praziquantel
or Albendazole (PI: Theodore E. Nash, MD, NIAID). Fifteen healthy subjects will be recruited.

For whole body scan using [(18)F]FBR, additional 30 healthy subjects will be recruited.
Therefore, total accrual numbers are 10 patients with neurocysticercosis and 45 healthy
subjects (15 for brain [(18)F]FBR and 30 for whole body [(18)F]FBR scans.

Design

Ten patients with neurocysticercosis and 15 age-matched healthy subjects will have brain PET
scans. In addition, we will also perform a whole body PET scan on 30 healthy subjects to
study the radiation-absorbed doses and study whether some healthy subjects do not show
binding of [(18)F]FBR. Patients will have up to three [(18)F]FBR PET scans during the
follow-up and the treatment under 85-I-0127, typically a few weeks apart.

Outcome measures



In brain PET scans, [(18)F]FBR binding will be compared with clinical symptoms and MRI
findings. In addition, the binding will be compared between patients and age-matched control
subjects. We have calculated radiation absorbed doses in approximately seven healthy subjects
who showed normal distribution (i.e., binders) of activity in organs. If we found subjects
who appear to have no binding to [(18)F]FBR, we will calculate radiation-absorbed doses of
the non-binders.

- INCLUSION CRITERIA:

COMMON TO PATIENTS WITH NEUROCYSTICERCOSIS AND HEALTHY SUBJECTS:

Ages between 18 and 65, inclusive.



In addition, patients must meet the inclusion criteria of protocol 85-I-0127.

Control subjects are healthy based on history, physical exams, ECG, and lab tests.

EXCLUSION CRITERIA:

COMMON TO ALL SUBJECTS:

Current psychiatric illness, substance abuse or severe systemic disease based on history
and physical exam.

ECG with clinically significant abnormalities. Any existing physical exam and ECG within
one year will be reviewed and if none already exists in the chart, these will be obtained
and reviewed.

Prior participation in other research protocols or clinical care in the last year such that
radiation exposure would exceed the annual guideline of RSC.

Pregnancy or breast feeding.

Claustrophobia.

Positive HIV test.

Cannot lie on back for a few hours for the PET scans.

ADDITIONAL EXCLUSION CRITERIA TO BRAIN SCANS:

Presence of ferromagnetic metal in the body or heart pacemaker.

[(18)F]FBR did not show binding in a whole body PET [(18)F]FBR scan in the past.

ADDITIONAL EXCLUSION CRITERIA FOR PATIENTS:

Medically unstable.

Seizures are not well controlled with medications.

A history of brain disease other than neurocysticercosis.

Laboratory tests with clinically significant abnormalities unrelated to neurocysticercosis
or its treatment.

ADDITIONAL EXCLUSION CRITERIA FOR HEALTHY SUBJECTS:

Laboratory tests with clinically significant abnormalities.

A history of brain disease.