Brief Summary

This study tests the radiolabeled molecule ("tracer"), \[¹¹C\]HSP990, using positron emission tomography (PET) imaging to assess whether it can be used to measure levels of Heat Shock Protein 90 (Hsp90). The protein Hsp90 plays an important role in how proteins in the brain fold into their three-dimensional structure and how this protein helps maintain cellular homeostasis. Since neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are characterized by disrupted three-dimensional protein folding resulting in protein aggregation, we also aim to measure Hsp90 levels in patients with these conditions.

\[¹¹C\]HSP990 is a promising tracer for this purpose and has already been extensively tested in animal models with safe and favorable results. The investigator now aims to evaluate this tracer in the human brain in healthy volunteers as well as in patients with Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. The investigator expects that Hsp90 protein levels will be present at reduced concentrations in patients, possibly in different brain regions depending on the distribution of the disease-causing proteins associated with these disorders.

Since the discovery of the important role of Hsp90 in neurodegenerative diseases, several candidate drugs targeting Hsp90 have been developed in recent years. The imaging method used in this study may support the development of Hsp90-targeting medications by enabling measurement of Hsp90 levels in the brain and assessment of the effects of these drugs.

Conditions

• Parkinson's Disease (PD)
• Alzheimer's Disease (AD)
• Amyotrophic Lateral Sclerosis (ALS)

Intervention / Treatment

• Other: [11C]HSP990 PET dosimetry
• Other: [11C]HSP990 PET test-retest
• Other: [11C]HSP990 simplified scan protocol

Primary Outcome Measures

• Quantification of HSP90 in the human brain (This will be assessed right after each scan in cohort 2 and 3. (Estimated visit lenght in cohort 2 will be 4 hours for each scanning procedure. In cohort 3 this will be optimized based on the results of cohort 2.))
  To quantify and compare Hsp90 levels in vivo in the human brain of healthy volunteers and patients with neurodegenerative disorders using the novel PET radioligand \[11C\]HSP990.

Countries

Belgium

Locations and Investigators

• UZ Leuven, Leuven, Belgium (Recruiting)
  • Koen Van Laere, MD, PhD, DSc

Study Officials

• Koen Van Laere (Principal Investigator) — KU Leuven