Usually, doctors monitor kidney cancer with CT scans to measure the size of tumors. Sometimes, even when a drug is working, it can take several months before the effects are seen on a regular CT scan. The purpose of this study is to see if a new kind of scan, called 124I-cG250 PET/CT, can determine response to sunitinib or pazopanib earlier than a regular CT scan.

Research has shown that certain proteins in the blood, called antibodies, can attach themselves to cancer cells without binding to normal cells. In this study, an antibody is used called chimeric G250 (cG250) that is attached to a radioactive isotope. The radioactive isotope in this study is Iodine-124 (124I). If cG250 has attached to tumors in the body, 124I shows up on the PET scan.

Inclusion Criteria:

• Histologically confirmed clear cell carcinoma (conventional) with advanced and/or metastatic disease.
• Radiographic evidence of unidimensionally measurable disease. Lesions will be considered measurable or non- measurable as per definitions provided in RECIST version 1.1
• Subjects must be planned for treatment with approved treatment doses of a VEGF receptor TKI (e.g., sunitinib, pazopanib, cabozantinib, axitinib, sorafenib, lenvatinib).
• Male or female, 18 years of age or older.
• ECOG (Eastern Cooperative Oncology Group) performance status of ≤ 2.
• Resolution of all acute toxic effects of prior chemotherapy, radiotherapy, or surgical procedure to NCI CTCAE grade ≤2.
• The following laboratory results should be within the following limits, within 2 weeks prior to study start:
• Absolute neutrophil count (ANC) ≥1.5 x 109/L
• Total serum bilirubin <2.0 mg/dL
• Platelets ≥100,000/μL
• Serum creatinine ≤2.0 mg/dL
• Aspartate aminotransaminase (AST) ≤ 2.5 x ULN (≤ 5.0x in case of liver mets)
• Alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5.0x in case of liver mets)
• Valid written informed consent signed by the patient prior to any study-specific procedures.

Exclusion Criteria:

• Women who are pregnant or breast-feeding. Female patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. A negative pregnancy test is required within 24 hours of administration of radiotracer and study initiation for women of childbearing age and potential.
• Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.
• Prior treatment with a VEGF receptor TKI within a time period equivalent to 5 half-lives of the prior TKI (e.g., there should be no substantial amount of TKI remaining in the patient).
• Patient is unable to undergo contrast-enhanced CT.
• Uncontrolled or unstable hyperthyroidism or Grave's Disease.
• Contraindication to IOSATTM intake (see package insert).
• Uncontrolled active seizure disorder or history of cerebrovascular accident (CVA) or transient ischemic (TI) attack within the past 12 months.
• Unstable cardiac disease, e.g., unstable angina, congestive heart failure or myocardial infarction within the preceding 6 months.
• Known active hepatitis B/C or HIV (human immunodeficiency virus) infection.
• Prior exposure to murine proteins or chimeric antibodies.