Positron Emission Tomography (PET) Imaging Studies With NIS Reporter

First In-human PET Imaging Studies With NIS Reporter [18F]BF4

The goal of this proposal is to perform first-in-man evaluation of and experimental imaging agent F-18 tetrafluoroborate (BF4) or (TFB).

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.

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:

  1. cardiac surgery or myocardial infarction within the last 6 months;
  2. unstable angina;
  3. coronary artery disease that required a change in medication within the last 3 months;
  4. decompensated congestive heart failure;
  5. 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;
  6. severe mitral or aortic valvular disease;
  7. uncontrolled high blood pressure;
  8. congenital heart disease;

• History of drug or alcohol abuse within the last year, or prior prolonged history of abuse;

• Clinically significant infectious disease, including AIDS or HIV infection or previous positive test for hepatitis B, hepatitis C, HIV-1, or HIV-2;

• Women of childbearing potential must not be pregnant (negative urine Human Chorionic Gonadotropin (β-HCG) at the time of screen) or lactating over the course of the study. A commercial urine dipstick test will be performed within 48 hours prior to injection of [18F]BF4 unless the screening urine pregnancy test falls within 48 hours of injection.

• Volunteers who, in the opinion of the investigator, are otherwise unsuitable for a study of this type;

• History of severe drug allergy or hypersensitivity; or

• Volunteers who had received an investigational medication within the last 30 days or who have participated in a clinical trial with any experimental medication or radiopharmaceutical in the last 30 days. Additionally, the time between the last dose of the previous experimental medication and enrollment (completion of screening assessments) must be at least equal to 5 times the terminal half-life of the previous experimental medication.

• Volunteers who are taking drugs with narrow therapeutic windows, such as theophylline, or warfarin, heparin and other anticoagulant therapies