First In-human PET Imaging Studies With NIS Reporter [18F]BF4
Overview
- Phase
- Phase 1
- Intervention
- BF4
- Conditions
- Myeloma
- Sponsor
- Mayo Clinic
- Enrollment
- 8
- Locations
- 1
- Primary Endpoint
- Evaluation of Tissue Distribution of F-18 BF4 in Healthy Volunteers
- Status
- Terminated
- Last Updated
- 6 years ago
Overview
Brief Summary
The goal of this proposal is to perform first-in-man evaluation of and experimental imaging agent F-18 tetrafluoroborate (BF4) or (TFB).
Detailed Description
F-18 tetrafluoroborate (BF4) or (TFB) is being used as a PET (Positron Emission Tomography) imaging biomarker for expression of the human sodium/iodide symporter (hNIS) in tissues. Imaging of functional hNIS activity in tissues with \[18F\]BF4 is anticipated to provide superior sensitivity and image quality to I-123 or Tc-99m SPECT for monitoring hNIS transduction effected by viral therapies. The proposed work is designed to 1) evaluate its safety, biodistribution, metabolism and radiation dosimetry characteristics in 8 healthy human volunteers and 2) evaluate the imaging feasibility in comparison with I-123 or Tc-99m SPECT of hNIS expression in a) 10 myeloma patients treated with Edmonston Measles virus-NIS (MV-NIS) and b) 10 endometrial cancer patients treated with vesicular stomatitis virus engineered to express human interferon and NIS (VSV-hINF-NIS). This data will be necessary to support future regulatory submissions.
Investigators
Tim DeGrado
PI
Mayo Clinic
Eligibility Criteria
Inclusion Criteria
- •Four male and four female healthy volunteers, greater than 21 years of age.
- •Subjects must provide written informed consent.
- •Willingness to provide all biological specimens as required by the protocol
Exclusion Criteria
- •Volunteers with any of the following are ineligible to enroll in this study:
- •Have currently clinically significant cancer, neurologic, hepatic, renal, pulmonary, metabolic, or endocrine disturbances, especially thyroid disease;
- •Current clinically significant cardiovascular disease. Clinically significant cardiovascular disease usually includes one or more of the following:
- •cardiac surgery or myocardial infarction within the last 6 months;
- •unstable angina;
- •coronary artery disease that required a change in medication within the last 3 months;
- •decompensated congestive heart failure;
- •significant cardiac arrhythmia or conduction disturbance, particularly those resulting in atrial or ventricular fibrillation, or causing syncope, near syncope, or other alterations in mental status;
- •severe mitral or aortic valvular disease;
- •uncontrolled high blood pressure;
Arms & Interventions
Healthy Volunteers
At the study visit, healthy subjects will have an initial physical exam, urine pregnancy test (if applicable) and will have catheters placed for i.v. drug administration and blood sampling. Vital signs, and blood samples will be obtained. Subjects will receive an infusion \[18F\]BF4 over 1 minute and PET imaging will begin. Three (3) PET/CT scanning procedures will be performed over a period of approximately 4 hours with two rest breaks in between. Venous blood samples for clinical laboratory tests will be taken before radiotracer administration and at 1.5 hours post-administration of radiotracer. In addition, venous blood samples will be taken during the PET/CT scans to determine blood pharmacokinetics and metabolite evaluation. Physical exam will be repeated at the end of the study.
Intervention: BF4
Myeloma patients
For cancer patients undergoing virus treatments, subjects will undergo \[18F\]BF4-PET/CT imaging at baseline before virus administration and at day 9 following virus treatment. Subjects will be screened by physician specialists within their clinics. Subjects who qualify for the study will return to the clinic within 30 days of screening, have a urine pregnancy test (if applicable) and will have catheters placed for i.v. drug administration. Vital signs will be obtained. All subjects will then receive a single i.v. bolus of \[18F\]BF4 for injection and PET/CT imaging will begin. Biopsies will be performed to confirm NIS expression in tissue of tumor regions showing uptake of \[18F\]BF4 in up to three myeloma patients when the site is accessible for biopsy.
Intervention: BF4
Endometrial cancer patients
For cancer patients undergoing virus treatments, subjects will undergo \[18F\]BF4-PET/CT imaging at baseline before virus administration and at day 9 following virus treatment. Subjects will be screened by physician specialists within their clinics. Subjects who qualify for the study will return to the clinic within 30 days of screening, have a urine pregnancy test (if applicable) and will have catheters placed for i.v. drug administration. Vital signs will be obtained. All subjects will then receive a single i.v. bolus of \[18F\]BF4 for injection and PET/CT imaging will begin. Biopsies will be performed to confirm NIS expression in tissue of tumor regions showing uptake of \[18F\]BF4 in up to three endometrial cancer patients when the site is accessible for biopsy.
Intervention: BF4
Outcomes
Primary Outcomes
Evaluation of Tissue Distribution of F-18 BF4 in Healthy Volunteers
Time Frame: 0-240 minutes
F-18 BF4 concentrations in major tissues (e.g., heart, blood pool, lung, liver, thyroid, stomach, kidney, brain, muscle) will be evaluated from the PET images from 0-240 minutes post-administration. Results will be used to compute radiation dosimetry estimates.
Secondary Outcomes
- Amount of Imaging Agent in Tumor (Uptake) in Myeloma and Endometrial Cancer Patients(Baseline, Day 9)