Summary: 

[18F]ACI-19626 is a special substance that, when injected into the bloodstream, travels to the brain and "lights up" areas where a disease-associated protein called TDP-43 has collected. Doctors can then see those areas using a brain scan called a PET scan. In healthy brains, TDP-43 works normally to help cells function. But in some diseases, TDP-43 clumps together in ways that damage brain and nerve cells. These clumps are found in nearly all people with ALS, about half of people with FTD, and in a condition called LATE (Limbic-Predominant Age-related TDP-43 Encephalopathy). Until now, there has been no reliable way to detect these clumps in a living person's brain. This study is the first time [18F]ACI-19626 has been tested in humans. The goal is to find out whether it is safe, how the body processes it, and whether it can accurately show TDP-43 buildup on a brain scan.

Who is eligible?

This study includes both patients and healthy volunteers and is divided into three parts:

Part 1:

• Healthy volunteers and people with a genetic form of FTD (frontotemporal dementia - GRN or C9orf72)

Part 2:

• Individuals diagnosed with FTD, ALS, or LATE including 
  
  • genetic carriers (GRN, C9orf72, or others associated with TDP-43 pathology)
  • Individuals with sporadic disease
• Asymptomatic genetic carriers (GRN, C9orf72, or others associated with TDP-43 pathology)
• Additional healthy volunteers

Part 3:

• Up to 5 people from Parts 1 or 2 who will come back for a second brain scan about one month after their first, to check whether the results are consistent

All patients, regardless of group must:

• able to provide informed consent 
• Either be beyond childbearing potential or using birth control during the study and for at least 30 days after the PET scan for women and 90 days after the PET scan for men.
• Able to lie in the scanner for up to 120 minutes.
• Healthy volunteers must 
  
  • be between the ages of 40 and 70, 
  • have no personal history of neurological or psychiatric disorder
  • have no family history of TDP-43 proteinopathies including FTD, ALS or other neurological conditions
  • Have no cognitive impairment based on cognitive assessment
• Individuals with FTD, ALS, or LATE must meet clinical criteria specific to diagnosis (e.g. Clinical Dementia Rating® plus National Alzheimer's Coordinating Center frontotemporal lobar degeneration global score ≥ 0.5)

Interested individuals meeting the above requirements should contact the study coordinator for additional requirements and exclusions if interested in participating.

What will happen during the study?

Participants will have 2 visits - the first visit will include consent and the eligibility screen (physical and neurological examinations, questionnaires, blood and urine tests, ECG and MRI in some cases).

At the second visit participants will receive the tracer [18F]ACI-19626 intravenously and be scanned in a PET scanner, during which blood will be collected.

Participants will also receive a phone call 2 to 4 days after the PET scan to report any symptoms and side-effects.

What are they measuring?

• Whether [18F]ACI-19626 is safe and well tolerated
• How quickly the substance reaches the brain and leaves the body
• Whether the brain scan can tell the difference between patients and healthy volunteers
• How much radiation exposure participants receive
• Whether scan results are consistent if the same person is scanned twice (Part 3 only)

How long will participants be involved?

Most participants will have one visit for the injection and scan. People in Part 3 will have two visits, about one month apart. This is not a long-term study; there is no ongoing treatment or follow-up.