The purpose of this protocol is to measure peripheral benzodiazepine receptors in the brain using positron emission tomography (PET) and compare the imaging results between patients and healthy people.

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 much greater levels of PBR than in microglia in resting conditions. 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, [(11)C]N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine (PBR28), which showed much greater specific signal than [(11)C]PK11195 in non-human primates.

The major objective of this protocol is to assess the utility of [(11)C]PBR28 PET to detect neuroinflammation in patients with neurocysticercosis.

In other protocols using [(11)C]PBR, 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

Thirty 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.

To avoid performing a brain scan with arterial blood sampling without getting usable data, each subject will have a screening [11C]PBR28 whole body scan with a low injection activity of 6 mCi and a short scan of approximately 1 h.

Design

After confirming binding of PBR28 in a whole body scan, the first 15 patients with neurocysticercosis and the first 15 age-matched healthy subjects will have brain PET scans. 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

PBR28 binding will be compared with clinical symptoms and MRI findings. In addition, the binding will be compared between patients and age-matched control subjects because the high levels of specific binding may allow detection of an increase of PBR in regions where MRI does not detect inflammation.

• Neurocysticercosis
• Healthy

• Anholt RR, De Souza EB, Oster-Granite ML, Snyder SH. Peripheral-type benzodiazepine receptors: autoradiographic localization in whole-body sections of neonatal rats. J Pharmacol Exp Ther. 1985 May;233(2):517-26.
• Anholt RR, Murphy KM, Mack GE, Snyder SH. Peripheral-type benzodiazepine receptors in the central nervous system: localization to olfactory nerves. J Neurosci. 1984 Feb;4(2):593-603.
• Anholt RR, Pedersen PL, De Souza EB, Snyder SH. The peripheral-type benzodiazepine receptor. Localization to the mitochondrial outer membrane. J Biol Chem. 1986 Jan 15;261(2):576-83.

• INCLUSION CRITERIA:

COMMON TO PATIENTS WITH NEUROCYSTICERCOSIS AND HEALTHY SUBJECTS:

Ages between 18 and 65, inclusive.

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.

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.