The goal of this clinical trial is to test whether we can reliably and safely measure the accumulation of pathological protein TDP-43 \[involved in rare forms of dementia such as frontotemporal dementia (FTD) and in amyotrophic lateral sclerosis (ALS)\] using a new positron emission tomography (PET) tracer called \[18F\]ACI-19626. Both healthy people and people with (suspected) TDP-43 accumulation will participate to this trial.
The main questions it aims to answer are:
* whether \[18F\]ACI-19626 is safe and well tolerated when injected into participants * whether \[18F\]ACI-19626 reliably detects abnormal TDP-43 in the brain using PET technique. * whether there are differences in the amount of this protein between people with diseases related to TDP-43 accumulation in the brain and people without these diseases.
Participants will:
* Visit the clinic to consent to their participation and to ensure they are eligible (physical and neurological examinations, questionnaires, blood and urine tests, ECG and MRI in some cases). * Visit the clinic to receive the tracer \[18F\]ACI-19626 intravenously and be scanned in a PET scanner, during which blood will be collected. * Receive a phone call from the clinic 2 to 4 days after the PET scan to report any symptoms and side-effects that they may be having.
Some of the participants may be asked to come again to the clinic for a second PET scan, allowing the researchers to determine if the measurements with the first PET scan are stable and reproducible.
Subject is able to provide written informed consent (IC), which must be obtained before any assessment is performed.
Female subjects must not be of childbearing potential, or if they are of childbearing potential to agree to use reliable contraception method(s) and not donate eggs for 30 days after the PET scan. Subjects without documentation of non-childbearing potential will perform serum pregnancy testing at screening and urine pregnancy test before the PET scan. A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the PI (e.g., Müllerian agenesis). Women of childbearing potential must commit to remain abstinent (refrain from heterosexual intercourse) or use a reliable form of birth control (e.g. a barrier, hormonal contraception method or intrauterine device), during the study and until 30 days after the last PET scan. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. Women of childbearing potential must commit to not donate ovum during the study and until 30 days after the last PET scan.
Male subjects with their partners of childbearing potential must commit to the use of a barrier method of contraception during the study and until 90 days after the last PET scan.
Male subjects must commit to not donate sperm during the study and until 90 days after the last PET scan.
Current or prior history of any alcohol or drug abuse in the past 2 years.
Laboratory tests with clinically significant abnormalities and/or clinically significant unstable medical condition.
Known history of hypersensitivity, including hypersensitivity to the active substances used for [18F]ACI-19626 or derivatives, or to any of the associated excipients.
Prior participation in other research protocols or clinical care during the past year that would result in radiation exposure to an effective radiation dose exceeding the acceptable annual limit (including the procedures in this clinical protocol).
AC Immune SA
Lead sponsor
Amsterdam UMC, location VUmc
Collaborator