This pilot clinical trial studies aldesleukin imaging in viewing tumor growth in patients with stage IV melanoma receiving ipilimumab or pembrolizumab therapy. Diagnostic procedures, such as single-photon emission computed tomography (SPECT), uses radioactive drugs and a scanner to make detailed pictures of areas inside the body and may be a less invasive way to check for stage IV melanoma. Radioactive drugs, such as technetium Tc 99 hydrazinonicotinamide-tricine-linked interleukin-2, carry radiation directly to cancer cells and may be able to differentiate between tumor growth due to inflammation versus tumor progression in patients with stage IV melanoma receiving therapy.

PRIMARY OBJECTIVES:

I. Feasibility/biodistribution of 99mTc-HYNIC-IL2 (technetium Tc 99 hydrazinonicotinamide-tricine-linked interleukin 2) scintigraphy in patients with metastatic melanoma undergoing immunotherapy with either ipilimumab (commercial source) or pembrolizumab.

SECONDARY OBJECTIVES:

I. Correlation of tumor infiltrating lymphocyte (TIL) invasion (scintigraphy/histology) with tumor burden; and description of any clinical side effects associated with imaging.

TERTIARY OBJECTIVES:

I. Correlation of TIL invasion assessed by 99mTc-HYNIC-IL2 scintigraphy vs. histology (total and subsets of TIL), as well as screen for peripheral blood correlates.

OUTLINE: Patients are assigned to 1 of 2 groups. COHORT I: Patients undergo technetium Tc 99 hydrazinonicotinamide-tricine-linked interleukin-2 scintigraphy prior to receiving ipilimumab or pembrolizumab and at 12 weeks.

COHORT II: Patients undergo technetium Tc 99 hydrazinonicotinamide-tricine-linked interleukin-2 scintigraphy prior to receiving ipilimumab or pembrolizumab, at 3-4 weeks, and at 12 weeks.

After completion of study treatment, patients are followed up at 30-45 days.

Inclusion Criteria:

• Pathologic proof of stage IV melanoma (pathology report confirmation) with plans to initiate therapy with ipilimumab or pembrolizumab according to Food and Drug Administration (FDA) approved guidelines, with multiple lesions such that

  • Two of these lesions are in the same organ and at least one of these two lesions is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 using either intravenous (IV) contrast enhanced computed tomography (CT) or CT component of positron emission tomography (PET)/CT OR
  • Three of these lesions are in different organs and at least one of these 3 lesions is measurable by RECIST 1.1 using either IV contrast enhanced CT or CT component of PET/CT

• Patient eligible for and will be receiving ipilimumab or pembrolizumab as standard of care therapy

• Absolute neutrophil count (ANC) >= 1500 mL

• Hemoglobin (Hgb) > 10 g/dL

• Platelets (PLT) >= 50,000 mL

• Aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN)

• Alkaline phosphatase =< 3 x ULN; up to 5 x allowed for patients with liver metastases

• Ability to provide informed consent

• Willingness to return to Mayo Clinic Rochester for follow-up

• Life expectancy >= 12 weeks

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

• For women of childbearing potential, a negative serum pregnancy test =< 7 days prior to registration

• Willingness to participate in mandatory imaging studies as well as provide mandatory blood samples for correlative research

• Tumor accessible for biopsy

Exclusion Criteria:

• Uncontrolled or current infection

• Known allergy to 99mTc-HYNIC-IL2 or components

• Any of the following prior therapies with interval since most recent treatment:

  • Chemotherapy =< 3 weeks prior to registration
  • Biologic therapy =< 3 weeks prior to registration
  • Radiation therapy =< 3 weeks prior to registration

• Failure to recover from side effects of prior chemotherapy or surgery

• Any of the following:

  • Pregnant women
  • Nursing women
  • Women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.)