Quantification of Hsp90 in the Human Brain

Inclusion criteria

• Healthy controls
• Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures
• Use of highly effective methods of birth control; defined as those that, alone or in combination, result in low failure rate (i.e., less than 1% per year) when used consistently and correctly; such as implants, injectables, combined oral contraceptives, some IUDs, true sexual abstinence (i.e. refraining from heterosexual intercourse during the entire period of risk associated with the Trial treatment(s)) or commitment to a vasectomised partner.
• Male or female subjects, age between 18-55 (Part 1, n = 3), 18-40 (Part II, n = 5) or 40-70 (Part III, 40-55 n = 5, 55-70 n = 5) years old.
• Subject is judged to be in good health by the investigator on the basis of medical history, physical examination including vital signs, clinical laboratory test and urinalysis.
• No history or evidence of current major neurological, internal or psychiatric disorder, based on the medical assessment as described hereabove and neuropsychological assessment (SCL-90).
• (Part II and III only: ) In subjects \< 60 years of age, a normal structural MRI scan as assessed by expert radiologist. In subjects \>= 60 years of age white matter hyperintensities corresponding to a white matter lesion (WML) Fazekas score \< 2 on the Age-Related White Matter changes scale are acceptable
• Parkinson's disease
• Age 45-85 years.
• Patient has clinically established PD based on the Movement Disorder Society (MDS) diagnostic criteria and is in Hoehn-Yahr stage I-III in the "on" medication state
• Patient has had a previous abnormal DaT-scan confirming the clinical diagnosis.
• Patient is able to understand the patient information brochure and give written informed consent
• Alzheimer's disease
• Age 45-85 years.
• MoCA score \< 26
• Patient has a diagnosis of probable AD with evidence of the AD pathophysiological process (amyloid PET scan or CSF determination) according to the consensus criteria \[McKahn et al 2011, Alzh Dement\].
• Patient is able to understand the patient information brochure and give written informed consent.
• Amyotrophic lateral sclerosis
• Age 20-85 years.
• Subjects will be recruited at the Neurology department of University Hospitals Leuven and must meet revised El Escorial Criteria and Awaji-Shima criteria for at least possible ALS.
• Patient is able to understand the patient information brochure and give written informed consent.

Exclusion criteria

• Healthy controls
• Participant has a history of any major disease that may interfere with the investigations or make the subject unfit for participation according to the interpretation by the investigator (especially diabetes mellitus, heart disease, liver and kidney disease, or most forms of cancer).
• Any prior or concomitant treatment(s) that might jeopardise the participant's safety or that would compromise the integrity of the Trial .
• Participation in an interventional Trial with an investigational medicinal product (IMP) or device.
• Evidence of cognitive impairment.
• Subject has a history or evidence of psychiatric disease.
• Subject has renal impairment with eGFR \< 60 ml/min.
• Subject is currently a user (including ''recreational use'') of any illicit drugs, including cannabis, or has a history of drug or alcohol abuse.
• (Part II and III only: ) Subject has a contra-indication for MRI scanning.
• Subject has a known hypersensitivity to any of the excipients that are present in the radiopharmaceutical preparations or to any of the excipients listed in the IMPD for \[11C\]HSP990.
• Subject suffers from claustrophobia or cannot tolerate confinement during PET-MRI scanning procedures. Subject cannot lie still for at least 70 minutes inside a scanner.
• Subject is unwilling to avoid unusual, unaccustomed, or strenuous physical activity (i.e., weightlifting, running, bicycling) from the time of the pre-study visit until the end of scanning;
• Subject does not understand the study procedures.
• Subject is unwilling or unable to perform all of the study procedures or is considered unsuitable in any way by the principal investigator.
• Subject is pregnant (according to Ulti Med hCG urine test) or is breastfeeding.
• Subject is a woman of childbearing potential who does not agree to apply appropriate contraception methods during study participation and continues to do so for at least 6 months after study completion. For WOCBP: contraception methods with a relatively high Pearl index (natural methods, minipill outside postpartum period, spermicides or condoms in monocontraception or no usage of contraception when sexually active) are not accepted.
• Subject is a man with a pregnant or non-pregnant WOCBP partner, who does not agree to use a condom and continue to do so until 90 days after study completion. In addition, the non-pregnant WOCBP partner should use a highly effective method of contraception.
• Subject does not agree that incidental findings are communicated to the general practitioner and to the participant him/herself.
• (Part II and III only: ) An abnormal Allen test or hypersensitivity/allergy to lidocaine.
• (Part II and III only: ) Anticoagulant therapy is an exclusion criterium for undergoing arterial sampling as part of the study. Subjects that have anticoagulant therapy can participate in the study parts without arterial sampling.
• Parkinson's disease:
• Neuropsychiatric diseases other than the cohort inclusion condition
• Major internal medical comorbidity, in particular diabetes or heart disease
• Subject has renal impairment with eGFR \< 60 ml/min.
• White matter lesion load on FLAIR Fazekas score 2 or higher or other relevant MRI abnormalities
• History of alcohol abuse or current alcohol abuse (chronic use of more than 15 units per week) or drug use
• Contraindications for MR
• Subject has a known hypersensitivity to any of the excipients that are present in the radiopharmaceutical preparations or to any of the excipients listed in the IMPD for \[11C\]HSP990.
• Subject suffers from claustrophobia or cannot tolerate confinement during PET scanning procedures; subject cannot lie still for 70 minutes inside the scanner.
• Subject is unwilling to avoid unusual, unaccustomed, or strenuous physical activity (i.e., weightlifting, running, bicycling) from the time of the pre-study visit until the end of scanning.
• Subject does not understand the study procedures or does not have a guardian who understands the study procedures.
• Subject (or guardian) is unwilling or unable to perform all of the study procedures or is considered unsuitable in any way by the principal investigator.
• Subject does not agree that incidental findings are communicated to the general practitioner and to the participant him/herself.
• Subject is pregnant (according to Ulti Med hCG urine test) or breastfeeding.
• Subject is a woman of childbearing potential who does not agree to apply appropriate contraception methods during study participation and continues to do so for at least 6 months after study completion. For WOCBP\* : contraception methods with a relatively high Pearl index (natural methods, minipill outside postpartum period, spermicides or condoms in monotherapy or no usage of contraception when sexually active) are not accepted.
• Subject is a man with a pregnant or non-pregnant WOCBP partner, who does not agree to use a condom and continue to do so until 90 days after study completion. In addition, the non-pregnant WOCBP partner should use a highly effective method of contraception.
• Anticoagulant therapy is an exclusion criterium for undergoing arterial sampling as part of the study. Subjects that have anticoagulant therapy can participate in the study parts without arterial sampling.
• Alzheimer's disease:
• \- cf. Parkinson's Disease exclusion criteria
• Amytorphic lateral sclerosis:
• cf. Parkinson's Disease exclusion criteria
• Subject has confined upper motor neuron involvement (i.e. primary lateral sclerosis) or confined lower motor neuron involvement (i.e. progressive muscular atrophy).