• Binding of [F-18]FBR at peripheral benzodiazepine receptor.
  

Drug: [F-18]FBR
N/A

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.

In other protocols using a PET ligand with similar structure, [(11) C]PBR28, approximately 15% of subjects (3/approximately 20) did not show binding. The reason is not clear but may be caused by polymorphisms of PBR. To avoid doing PET scans for subjects who don't have binding, we will perform a screening whole body scan.

Study population

Twenty 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). Thirty healthy subjects will be recruited.

Prior to a brain [(18) F]FBR scan, each subject will have a screening [(11) C]PBR28 whole body scan with a low injection activity of 6 mCi and a short scan of approximately 1 h. We request permission to perform a screening [(11) C]PBR28 whole body scan on 20 patients and 20 healthy subjects.

Design

After confirming binding of PBR28 in a whole body scan, 10 patients with neurocysticercosis and 10 age-matched healthy subjects will have PET scans. In addition, we will also perform a whole body PET scan on 10 healthy subjects to study the radiation-absorbed doses. 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. In whole body scans, radiation-absorbed doses will be calculated based on the Medical Internal Radiation Dose scheme.

• 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.

AN ADDITIONAL EXCLUSION CRITERION TO BRAIN SCANS:

Presence of ferromagnetic metal in the body or heart pacemaker.

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.