The aim of this study is to measure the availability of the PDE10A enzyme in Huntington disease gene expansion carriers (HDGECs) using the recently developed radioligand [18F]MNI-659. The study will be cross-sectional, examining HDGECs at different stages of the disease (pre-manifest, stage 1 and stage 2), in comparison with Healthy Controls (HCs). The HDGECs included in this study will be recruited from the large database of the REGISTRY (NCT01590589) or ENROLL-HD (NCT01574053) studies.

The study will be organized in an "adaptive-like" mode. Initially a cohort of 5 HDGECs and 5 HCs will be studied. The data obtained in the first cohort will be analysed and depending on the variability of the data, there will be approximately 10 HDGECs and an equal number of HCs in the second cohort and the size of the third cohort may be altered to in total include approximately 45 HDGECs and an equal number of HCs.

Inclusion Criteria:

• Capacity to give full informed consent in writing, and have read and signed the informed consent
• Age 18 to 70 years, inclusive
• HCs: Healthy according to medical history, physical examination, ECG, vital signs, laboratory assessment and MRI, with a body mass index between 19 and 27 (both inclusive)
• HDGECs: Otherwise healthy according to medical history, no co-morbidity of psychotic disorders, physical examination, vital signs and laboratory assessments
• HDGECs:

(A) HD Stage 1 or HD Stage 2: Patients with a clinical diagnosis of HD, defined by the presence of noticeable motor disorder and 40 CAG repeats (HD stage 1: Total Functional Capacity (TFC) 11-13, HD stage 2: TFC 7-10); (B) Pre-manifest: Subjects that are carriers of the mutant Huntingtin gene with ≥40 CAG repeats, a disease burden score ≥ 275 (calculated by the equation ((CAGn-35.5) X age)), and a Total Motor Score (TMS) ≤ 5.

• Able and willing to travel to Stockholm
• Willing to comply with use of adequate contraceptive measures:

Exclusion Criteria:

• Any disease, condition or concomitant medications that significantly compromises the function of the body systems and that, in the opinion of the Investigator might interfere with the conduct of the study or the interpretation
• Regular use of any medication prohibited by this protocol with the exception for Viagra, Levitra and Cialis, which may be temporarily discontinued prior to the PET measurements
• HDGECs: History of other neurological condition (including brain surgery, intracranial haematoma, stroke/cerebrovascular disorders, epilepsy), co-morbidity of psychotic disorders
• HCs: Anamnesis/medical history of neurological conditions (Alzheimer´s disease, dementia, Parkinson´s disease, brain surgery, intracranial haematoma, stroke/cerebrovascular disorders, epilepsy) or psychiatric conditions schizophrenia, depression, bipolar disorder, attention-deficit hyperactivity disorder)
• HCs: Family history of HD
• History of or current alcohol or drug abuse or dependence
• History of anaphylactoid or anaphylactic reactions to any allergen including drugs and contrast media
• Haematological or biochemical parameters that are outside the normal range and are considered clinically significant by the Investigator
• Clinical relevant findings in the 12-lead ECG as determined by the evaluating physician
• Donation of blood (450 mL) within three months prior to Visit 3
• Contraindication to MRI, such as known claustrophobia, presence of metal devises or implants (e.g. pacemaker, vascular- or heart- valves, stents, clips), metal deposited in the body (e.g. bullets or shells), or metal grains in the eyes
• Participating in a clinical trial within the past 3 months
• HCs: previous participation in another PET study
• Positive viral test result for Hepatitis B or C or HIV 1 or 2
• Female subjects: breast-feeding or positive pregnancy test at screening or at Visit 3
• Contraindication for arterial cannulation (by assessment of Allen's test)