Functional Microscale Organotypic Assays to Predict Patient Response to Anti-Angiogenesis Therapies

Response of anti-angiogenesis therapy will be quantified using PSMA-based PET imaging using a
novel agent,18F-DCFPyL, as a non-invasive imaging biomarker of tumor neovasculature to
functionally monitor renal cell cancer neovasculature in patients undergoing systemic
anti-angiogenesis therapy. PSMA PET will be compared with response to anti-angiogenesis
therapy using conventional imaging computed tomography(CT)-based RECIST1.1 criteria as well
as histopathological endpoints (tumor vascular density, immunohistochemical staining for PSMA
and neovascularization (cluster of differentiation(CD)105, CD31). Whole body PSMA PET/CT
scans will be obtained at baseline, following adjuvant anti- angiogenic therapy and when the
patient becomes refractory to treatment.

The rationale and time points for obtaining PET scans is planned with respect to the typical
natural history of metastatic RCC. This project will obtain information from tumors that are
responding to anti-angiogenesis therapy and those resistant to treatment.

Inclusion Criteria:

- Patients diagnosed with metastatic clear cell RCC as proven by biopsy.

- Adults, 18 years of age or older.

- Surgical candidates who have clinical indication for nephrectomy and standard-of-care
biopsy of metastatic disease followed by standard of care systemic anti-angiogenesis
treatment regimen

- Have consented to participate in the University of Wisconsin Carbone Cancer Center
Biobank.

Exclusion Criteria:

- Patients who have received prior RCC systemic therapies

- Prior history of prostate cancer

- Prior history of any other malignancy within the last 2 years, other than skin basal
cell or cutaneous superficial squamous cell carcinoma that has not metastasized and
superficial bladder cancer

- Unable to lie flat during or tolerate PET/CT

- Serum creatinine > 2 times the upper limit of normal