This study uses molecular imaging and novel immune monitoring to identify a biomarker of response for melanoma patients receiving immunotherapy with anti-PD-1 immunotherapy. Prior to treatment, FDG and FLT PET/CT will be obtained, together with blood and tumor biopsies from each patient. A follow-up FDG and FLT PET/CT will be obtained, together with blood and tumor biopsies, 10-12 weeks after starting treatment with anti-PD-1 antibody. Additional tumor biopsies and blood samples for immune monitoring will be obtained 4-6 weeks after starting treatment with anti-PD-1 antibody as well as 16-18 weeks after starting anti-PD-1 treatment for patients still receiving anti-PD-1 antibody at that time.

Inclusion Criteria:

• Participants must have a metastatic melanoma diagnosis (stage IV) for which treatment with nivolumab or pembrolizumab, either alone or in combination with other therapies, is planned. No additional laboratory testing is needed for the imaging in this study apart from the standard laboratory testing routinely obtained for treatment with nivolumab or pembrolizumab, either alone or in combination with other therapies.
• Participants must have at least 2 subcutaneous or lymph node melanoma metastases that are 2 cm in greatest diameter and are amenable to being biopsied in clinic without requiring image-guidance.
• Participants must be able to provide informed consent
• Women of childbearing potential must be willing to use effective contraception as discussed with their oncologist while participating in this study.

Exclusion Criteria:

• Not able to receive treatment with either nivolumab or pembrolizumab.
• Women of child-bearing potential must have a negative serum or urine pregnancy test within 7 days of the first study FLT PET/CT and must not be breast feeding for the duration of study participation.

Up to 4 metastatic melanoma patients will be recruited from the University of Wisconsin (UW) Carbone Cancer Center (CCC) Melanoma Clinic located in the UW-Hospital and Clinics.