PET Imaging of Peripheral Benzodiazepine Receptors in Patients With Neurocysticercosis Using [F-18]FB
Condition: Neurocysticercosis; Healthy
MeSH terms: Neurocysticercosis; Cysticercosis; Taeniasis
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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

      <TAB>

      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.
    

Intervention name(s): [F-18]FBR
Intervention type(s): Drug
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Epilepsy; Taenia Solium; Microglia; Neuroinflammation; Compartment Model; Neurocysticercosis; Healthy Volunteer; HV