F-18 TFB-PET Studies in Cancer Patients Undergoing NIS-containing Viral Therapies

The goal of this proposal is to perform first-in-man evaluation of the imaging probe F-18
tetrafluoroborate (BF4) as a PET 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 Tc-99m SPECT for monitoring
hNIS transduction effected by viral therapies. The proposed work is designed to 1) evaluate
the imaging feasibility in comparison with 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:

Myeloma Patients

1. Patients who are currently participating in Mayo Clinic MV-NIS trial (IRB: 06-005263)
and agree to enroll in additional 18F-TFB PET studies.

2. Subjects are greater than 21 years of age.

3. Subjects must provide written informed consent.

4. Agree to provide biopsy of tumor indicated on PET for research purposes, if
accessible.

Endometrial Cancer Patients

1 Patients who are currently participating in Mayo Clinic VSV-hINF-NIS trial (IRB
15-007000) and agree to enroll in additional 18F -TFB-PET studies.

2. Subjects are greater than 21 years of age. 3. Subjects must provide written informed
consent. 4. Agree to provide biopsy of tumor indicated on PET for research purposes, if
accessible.

Exclusion Criteria:

Myeloma Patients

Patients with any of the following are ineligible to enroll in this study:

1. 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. Before enrolling a patient with any of the above
conditions, the co- investigator must contact the principal investigator.

2. History of drug or alcohol abuse within the last year, or prior prolonged history of
abuse.

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

4. Women of childbearing potential must not be pregnant (negative urine 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-TFB PET unless the
screening urine pregnancy test falls within 48 hours of injection.

5. Patients who, in the opinion of the investigator, are otherwise unsuitable for a study
of this type.

6. History of severe drug allergy or hypersensitivity.

7. Patients who had received an investigational medication within the last 30 days or who
have participated in a clinical trial involving medications other than the related
MV-NIS or VSV-NIS viruses 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.

8. Patients with current clinically significant medical comorbidities that might pose a
potential safety risk, interfere with the absorption or metabolism of the study
medication, or limit interpretation of the study results. These include but are not
limited to clinically significant hepatic, renal, pulmonary, metabolic or endocrine
disease, cancer, HIV infection and AIDS.

9. Patients who are taking drugs with narrow therapeutic windows, such as theophylline,
or warfarin, heparin and other anticoagulant therapies.

Endometrial Cancer Patients

Patients with any of the following are ineligible to enroll in this study:

1. 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. Before enrolling a patient with any of the above
conditions, the co- investigator must contact the principal investigator.

2. History of drug or alcohol abuse within the last year, or prior prolonged history of
abuse.

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

4. Women of childbearing potential must not be pregnant (negative urine 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-TFB PET unless the
screening urine pregnancy test falls within 48 hours of injection.

5. Patients who, in the opinion of the investigator, are otherwise unsuitable for a study
of this type.

6. History of severe drug allergy or hypersensitivity.

7. Patients who had received an investigational medication within the last 30 days or who
have participated in a clinical trial with any experimental medication 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.

8. Patients with current clinically significant medical comorbidities, that might pose a
potential safety risk, interfere with the absorption or metabolism of the study
medication or limit interpretation of the study results. These include but are not
limited to clinically significant hepatic, renal, pulmonary, metabolic or endocrine
disease, cancer, HIV infection and AIDS.

9. Patients who are taking drugs with narrow therapeutic windows, such as theophylline,
or warfarin, heparin and other anticoagulant therapies.