PET Imaging of Peripheral Benzodiazepine Receptors in Patients With Neurocysticercosis Using [C-11]PBR28

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.

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.

Design

Fifteen patients with neurocysticercosis and the first 15 age-matched healthy subjects will
have brain PET scans. Patients will have up to three [(11)C]PBR28 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.

- INCLUSION CRITERIA:

Common to patients with neurocysticercosis and healthy subjects:

Ages between 18 and 75, 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.

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.

The usage of nonsteroidal and other anti-inflammatory medications is not an exclusion
criterion.