Radiotracer to detect regional tissue inflammation Other
Conditions
Interventions
PET-CT scan using [18F]LW223 radiotracer
Participants will undergo one PET-CT scan with duration between 2-6 hours depending on the cohort. During the scan, we will collect blood and/or urine samples
Sponsors
University of Edinburgh
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Male subjects between 18 and 55 years old, inclusive, at screening visit. 2. Provision of informed consent prior to any study-specific procedures. 3. Willing to undergo genotyping for the rs6971 genetic polymorphism to allow placement into the correct study cohort. 4. Must be surgically sterile (vasectomy) or practicing at least one of the following methods of contraception, and refrain from sperm donation, from radiopharmaceutical administration until 90 days after the radiopharmaceutical administration: a. Partner(s) using an intrauterine device; b. Partner(s) using hormonal contraceptives (oral, vaginal, parenteral or transdermal); c. Subject and/or partner(s) using double-barrier method (condoms, contraceptive sponge, diaphragm, or vaginal ring with spermicidal jellies or creams); d. Total abstinence from sexual intercourse as the preferred lifestyle of the subject; periodic abstinence is not acceptable. 5. Body Mass Index (BMI) between 18 to 35 kg/m², inclusive. BMI is calculated as weight in kilograms divided by the square of height measured in meters. 6. In good physical and mental health on the basis of medical history, physical examination, and routine laboratory measurements (i.e. without major or clinically relevant pathology), as judged by the Investigator. 7. For Cohort 2, subject is willing to allow the investigators to place an arterial catheter in the radial artery and has a readily palpable pulse. 8. Willing to refrain from consumption of caffeinated beverages from 48 hours prior to study radiopharmaceutical administration until the end of scanning session.
Exclusion criteria
Exclusion criteria: 1. Inability or unwillingness to give informed consent. 2. History of claustrophobia or inability to tolerate supine position for PET/CT scans, determined by participant questionnaire at screening. 3. Exposure to >10 mSv of ionizing radiation within the last 12 months, determined by reviewing data in the TOPS registry and electronic health records at screening. 4. Participation in more than 4 other drug trials in the 12 months prior to the study, determined by participant questionnaire and records review. 5. Receipt of an investigational product within a time period equal to 10 half-lives (if known), or within 6 weeks prior to the scanning visit. 6. Use of any over-the-counter medication, prescription medications, vitamins and/or herbal supplements within a time period equal to 6 half-lives (if known), or within 2 weeks prior to the scanning visit. 7. Self-assessed use of tobacco or other nicotine-containing products within 6 months preceding the screening visit, and a positive cotinine test at the scanning visit. 8. Self-assessed history of drug or alcohol abuse within 2 years prior to the screening visit. Alcohol abuse is defined as use of more than 28 units of alcohol per week or a positive drug/alcohol test at the scanning visit. 9. Known history of significant sensitivity or allergy to any drug, determined by questionnaire and records review. 10. Impaired renal function with eGFR 480 ms at screening, as determined by the investigator. 12. Positive test result for HAV-IgM, HBsAg, HCV Ab, or HIV Ab at screening. 13. Donation or loss of =400 mL blood volume (including plasmapheresis), or transfusion of any blood product <8 weeks prior to study start. 14. History of seizures (except single febrile seizure in childhood) or first-degree relative with confirmed epilepsy. 15. History of psychiatric diseases or disorders, determined by questionnaire and records review: a. Major depressive episode within past 2 years (DSM-IV-TR); b. Serious and persistent mental illness: bipolar disorder, schizophrenia, schizoaffective disorder, PTSD, OCD, or borderline personality disorder; c. Significant current suicidal ideation (C-SSRS questions 4 or 5), or any history of suicide attempts. 16. Known family history of long-QT syndrome or unexplained sudden death. 17. History of gastric surgery, cholecystectomy, vagotomy, bowel resection, or any procedure affecting GI motility, pH, or absorption. 18. Serious illness requiring hospitalisation or surgery within 30 days prior to study drug administration. 19. Individuals designated as classified persons under the Ionising Radiations Regulations 2017 by their employer. 20. Volunteers who completed participation in the [18F]LW223 TSPO PET radiotracer trial are not eligible for re-enrolment. 21. Volunteers who experience an adverse event during the screening visit will be excluded from the trial and will not proceed to the scanning visit. 22. If an adverse event occurs during the scanning visit before IMP administration, a clinician will assess eligibility to continue.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability based on the number and severity of adverse events at 27 months from approval | — |
Secondary
| Measure | Time frame |
|---|---|
| Utility of [18F]LW223 as a TSPO PET radiotracer at 27 months from approval defined based on: 1. [18F]LW223 effective dose measured in healthy adult males using whole-body biodistribution and pharmacokinetic studies 2. Low affinity binder (LAB) to high affinity binder (HAB) PET outcome measure ratio determined using quantitative kinetic modelling and uptake indices 3. Comparable binding kinetics in LAB, HAB and mix affinity binder (MAB) determined using quantitative kinetic modelling and uptake indices | — |
Countries
Scotland, United Kingdom
Contacts
Public ContactPhyo;Hannah Khaing;Costello
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Outcome results
None listed