Pembrolizumab TX-naive Distant Mets Melanoma and Use of (C11-AMT) PET at Baseline as Imaging Biomarker

Inclusion Criteria: 1. Sign written informed consent and HIPAA authorization for release of personal health information. Note: HIPAA authorization may be included in the informed consent or obtained separately. 2. Subject must be 18 years of age or more on the day of signing informed consent. 3. Have histologic or cytologic biopsy-proven diagnosis of unresectable stage III or distant metastatic melanoma, irrespective of histologic type (i.e. cutaneous, unknown primary, mucosal, or ocular). Patients with resectable bulky stage IIIB or stage IIIC melanoma (for example at least 2.5-cm in shortest diameter for lymph nodes infiltrated by tumor and at least 2-cm in longest diameter for non-lymph nodes infiltrated by tumor) can also be entered into the study at the discretion of the Principal Investigator. 4. Have measurable disease based on RECIST v1.1. for solid tumors 5. Be willing to undergo fresh tumor tissue biopsy of an accessible tumor lesion prior to pembrolizumab. A mandatory fresh biopsy will be collected following C11-AMT PET imaging. Subjects for whom fresh samples cannot be provided (e.g. inaccessible or subject safety concern) or do not agree to this fresh tumor research biopsy of accessible tumor will be deemed ineligible for study participation. Exception to the mandatory tumor tissue collection are patients with metastatic lung lesions as the only site of metastatic disease. Fresh biopsy collection from these subjects will be optional, due to high risk of pneumothorax. 6. Be willing to allow for investigators to collect archival tumor tissues from surgical procedures that may have been performed before or after enrollment into this trial for research purposes (in-house cases and/or outside cases). These samples will be obtained by study staff as long as subject continues on follow-up. Blocks of tissue will be requested, and if blocks are not able to be obtained, 5micron slides (10-15) will be sufficient. 7. Be willing to be injected with 11C-methyl-L-tryptophan (C11-AMT) 8. Have a performance status of 0 - 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. 9. Has not received prior therapy with cytotoxic T lymphocyte antigen (CTLA)-4, PD-1/PD-L1 inhibitors, other co-stimulatory or co-inhibitory immune checkpoint antibody therapies (e.g. LAG3, TIM3, cluster of differentiation (CD) 137, Killer immunoglobulin-like receptor (KIR3DL), cluster of differentiation (CD) 70, and CD27) for distant metastatic melanoma. Patients who have received mitogen-activated protein kinase (MAPK) inhibitors are allowed on condition that they have recovered from adverse events to at most Grade 1 by CTCAE v4.03 and at least 15 days have elapsed between last dose of MAPK inhibitors and C11-AMT imaging. Patients who have previously received CTLA-4 inhibitors in the adjuvant setting are allowed to participate as long as they discontinued CTLA-4 treatment at least 30 days ago and meet criteria outlined in inclusion #14. Patients who have previously received adjuvant PD-1 inhibitors are excluded. 10. Demonstrate adequate organ function as defined in below; all screening labs to be obtained within 14 days prior to C11-AMT PET scan: Hematological: Hemoglobin (Hgb) - ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of Hgb) Absolute Neutrophil Count (ANC) - ≥ 1,500/mm3 Platelets - ≥ 100,000/mm3 Renal: Serum Creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) - ≤1.5 x ULN OR ≥ 60 mL/min using the Cockcroft-Gault formula for subject with creatinine levels \> 1.5 X institutional upper limits of normal (ULN) Hepatic: Serum Total Bilirubin - ≤ 1.5 X ULN Aspartate aminotransferase (AST) - ≤ 2.5 X ULN OR \< 5 X ULN for subjects with liver metastases Alanine aminotransferase (ALT) - ≤ 2.5 X ULN OR \< 5 X ULN for subjects with liver metastases Albumin - ≥ 2.5 mg/dL Coagulation: International Normalized Ratio (INR) or Prothrombin Time (PT) - ≤1.5 X ULN, unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants Activated Partial Thromboplastin Time (aPTT) - ≤1.5 X ULN, unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants 11. Female subjects of childbearing potential should have a negative urine or serum pregnancy within 14 days prior to C11-AMT PET scan. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 12. Female subjects of childbearing potential must be willing to use adequate methods of contraception as outlined - Contraception for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. Male subjects should agree to use an adequate method of contraception as outlined - Contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. 13. Patients who have received prior adjuvant high dose interferon are allowed to participate as long as the last injection was given at least 30 days prior to the C11-AMT PET scan and they have fully recovered from side effects (i.e., Grade ≤1 or permanent side effects that require hormone replacement therapy). 14. Patients on adjuvant ipilimumab are allowed to participate at least 30 days from drug discontinuation as long as they have at most Grade 1 adverse events (or grade 2 if they have to received hormone replacement therapy for their otherwise grade 1 ipilimumab-induced autoimmune endocrinopathies). Exclusion Criteria: 1. Is currently participating and receiving study therapy for his/her advanced melanoma or has participated in a study of an investigational agent and received study therapy in the advanced melanoma setting. 2. Has received prior treatment with PD-1/PD-L1 pathway inhibitors in the adjuvant setting. 3. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to C11-AMT PET Scan 4. Has a known history of active tuberculosis (Bacillus Tuberculosis) 5. Hypersensitivity to pembrolizumab or any of its excipients described 6. Has had prior monoclonal antibody (mAb) targeting immune checkpoint proteins, for distant metastatic melanoma and have progressed or have developed intolerable side effect. 7. Adjuvant anticancer treatments are allowed at least 30 days has elapsed between the infusion/injection and C11-AMT PET scan as part of this study. 8. Prior radiation therapy for metastatic melanoma is allowed as long as the patient bears measurable actively growing disease outside the previously irradiated field. Note: If subject received major surgery, they must have recovered adequately from the toxicity (i.e., all symptoms ≤ grade 1) and/or complications from the intervention prior to starting therapy. 9. History of prior malignancy, with the exception of the following: * Non-melanoma skin cancers, non-invasive bladder cancer, and carcinoma in situ of the cervix, * Prior history of prostate provided patient not under active systemic treatment other than hormonal therapy and with documented undetectable prostate-specific antigen (PSA) (\<0.2ng/mL), * Chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) provided patient has isolated lymphocytosis (Rai stage 0), and does not require systemic treatment \[for "B" symptoms, Richter's transformation, lymphocyte doubling time (\<6 months), lymphadenopathy or hepatosplenomegaly\], * Lymphoma or any type or hairy-cell leukemia provided patient is not on active systemic treatment and is in complete remission, as evidenced by PET/CT scans and bone marrow biopsies for at least 3 months, * Papillary thyroid cancer. Since this malignancy very infrequently metastasizes distantly, patients with concurrent metastatic melanoma can be enrolled even if patients may: A) have just completed thyroidectomy within the last 2 years, B) have not received adjuvant radioactive iodine therapy, C) were only recently diagnosed with asymptomatic papillary thyroid cancer and their surgery is pending. * History of malignancy provided patient has completed therapy and is free of disease for ≥ 2 years. If patient had other malignancy within the last 2 years from which he may have been completely cured by surgery alone, he may considered to be enrolled on condition that the risk of development of distant metastatic disease based on AJCC staging system is less than 30%. 10. Has known active parenchymal central nervous system (CNS) metastases that are symptomatic, and/or more than one lesions, and/or their largest diameter is \> 5-mm and/or require antiepileptic drugs or corticosteroids. Patients with carcinomatous meningitis are also excluded. Exceptions are: subjects with previously treated brain metastases provided they are stable (without evidence of progression by imaging) for at least 2 weeks prior to C11-AMT and any neurologic symptoms have returned to baseline, have no evidence of new or enlarging brain metastases, and are not using ongoing steroids for at least 7 days prior to C11-AMT. Patients with active (i.e. not treated with stereotactive radiosurgery), single, asymptomatic, up to 5-mm in largest diameter brain metastases (measured either by brain MRI with IV contrast or head CT with IV contrast measured within 2 weeks prior to C11-AMT) are allowed. 11. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease-modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 12. Has known history of (non-infectious) pneumonitis that required steroids, or any evidence of current pneumonitis. 13. Has an active infection requiring systemic therapy. 14. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 15. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 16. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. 17. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 18. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C virus (HCV) (e.g., HCV RNA \[qualitative\] is detected). 19. Has received a live vaccine within 14 days of C11-AMT PET scan. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.