Imaging Studies of Kidney Cancer Using 18F-VM4-037

BACKGROUND:

- Carbonic Anhydrase IX (CA IX) is a hypoxia-inducible enzyme regulated by the Von Hippel
Lindau (VHL) protein that is commonly overexpressed in certain malignancies including
renal cell carcinoma (RCC) and may have prognostic significance.

- The VHL gene is commonly mutated or inactivated in RCC tumors and VHL activity
regulated the expression and activity of not only CAIX but also CAXII as well as other
genes critical for tumor angiogenesis such as vascular endothelial growth factor
(VEGF), glucose transporter 1 (GLUT1), glucose transporter 3 (GLUT 3) and platelet
derived growth factor (PDGF).

- 18F-VM4-037 is an imaging drug product formulation which binds to the active site
ligand of CA-IX and also binds to CAXII. We propose to evaluate 18F-VM4-037 as a
positron emission imaging (PET) radiopharmaceutical for the in vivo detection of CA-IX
and CAXII in renal tumors.

STUDY OBJECTIVES

PRIMARY OBJECTIVE:

- To evaluate the biodistribution of 18F-VM4-037 within tumor and non-tumor tissues.

- To assess safety of 18F-VM4-037 in patients with primary or metastatic RCC.

ELIGIBILITY:

- Subject is greater than or equal to 18 years old, Eastern Cooperative Oncology Group
(ECOG) 0-2.

- Subject must have confirmed primary RCC (greater than or equal to 2.5cm) in diameter on
conventional imaging modality or extrarenal/extrahepatic RCC lesion (greater than or
equal to 1cm).

DESIGN:

- Twenty subjects with primary RCC greater than or equal to 2.5cm in diameter or
extrarenal/extrahepatic lesion suspicious for metastatic RCC (greater than or equal to 1cm
in diameter) scheduled for clinically indicated surgery or biopsy will undergo dynamic
18F-VM4-037 PET/CT imaging. Results will be compared with pathology.

- INCLUSION CRITERIA:

- Subject is greater than or equal to18 years old.

- Subject must be scheduled to undergo surgery or biopsy for primary renal cell
carcinoma (RCC) greater than or equal to 2.5cm in diameter or extrarenal/extrahepatic
metastatic RCC lesion (greater than or equal to1cm in diameter) at the National
Institutes of Health (NIH) Clinical Center based on imaging within 3 weeks.

- Chemistry parameters: aspartate aminotransferase (AST) and alanine aminotransferase
(ALT) less than or equal to 2 times of the upper limits of normal; total bilirubin,
of < 2 times the upper limits of normal or < 3.0 mg/dl in patients with Gilberts
syndrome.

- Eastern Cooperative Oncology Group (ECOG) Performance score of 0 to 2.

- Ability to provide informed consent. All subjects must sign an informed consent form
indicating their understanding of the investigational nature and risks of the study
before any protocol-related studies are performed.

- The subject has a clinically acceptable medical history, physical examination and
vital signs findings during the screening period (from within 21 days before
administration of 18F-VM4-037). Components of an acceptable medical history include
no active infection at the time of enrollment or within 7 days of enrollment, no
prior therapy that results in immunocompromise or impaired renal function (serum
creatinine within 2 weeks prior to positron emission tomography (PET) imaging less
than or equal to1.8 mg/dl and epidermal growth factor receptor (eGFR) must be > 30
ml/min/1.73m^2) or findings indicating an inability to tolerate the requirements for
the scan. Previous exposure to immunocompromising therapy does not exclude the
patient; patients must have an absolute neutrophil count > 1.5/microL within 2 weeks
of PET imaging.

- If female, must have a negative serum human chorionic gonadotropin (HCG) within 24
hours prior to 18F-VM4-037 injection OR be post menopausal for > 2 years OR be
surgically sterile.

EXCLUSION CRITERIA:

- Subjects for whom participating would significantly delay the scheduled standard of
care therapy.

- Subjects with any coexisting medical or psychiatric condition that is likely to
interfere with study procedures and/or results.

- Subjects with severe claustrophobia unresponsive to oral anxiolytics.

- Other medical conditions deemed by the principle investigator (or associates) or
sponsor to make the subject ineligible for protocol procedures.

- Female subject is pregnant or nursing

- The site of the target lesion must not have been part of a radiation portal within 6
months of enrollment.

- Subjects having received another investigational agent within 1 month before
administration of 18F-VM4-037.