18F-Fluciclovine PET/CT in Multiple Myeloma

Background: Multiple myeloma (MM) is an incurable cancer of certain blood cells. MM often returns after treatment, and most people survive only 5 to 8 years after diagnosis. To improve survival, researchers need to find ways to identify returning disease earlier. Objective: To find out if the radiotracer 18F-fluciclovine (a substance injected into the blood during imaging scans) is better at detecting MM than the one (18F-FDG) currently used for this purpose. Eligibility: Adults aged 18 years or older with MM. The MM may be newly diagnosed (NDMM); or it may have returned or failed to respond after at least 1 prior line of treatment (RRMM). Design: Participants will be screened. They will have blood tests. They will have a positron emission tomography (PET) or computed tomography (CT) scan using 18F-FDG. The radiotracer will be injected into a vein. Then participants will lie on a table while the PET/CT scan takes images of their body. All participants will have 3 study visits. During each visit they will have: Two PET/CT scans. One with 18F-FDG, one with 18F-fluciclovine. An optional magnetic resonance imaging scan. A bone marrow biopsy. An area on the hip will be numbed; a needle will be inserted to draw out a sample of the soft tissue from inside the bone. These tests may be spread over 30 days for each visit. NDMM participants will have their second study visit 2 to 4 weeks after they complete their usual treatment for the disease. RRMM participants will have their second visit 6 months after their first. All participants will have a third study visit after 5 years or when their disease progresses.

* INCLUSION CRITERIA: * Participants must have a documented diagnosis of MM defined by the IMWG Criteria. Participants at diagnosis must have had a serum M-protein \>= 3 g/dL and/or bone marrow plasma cells \>= 10% and at least one of the following: * Anemia: Hemoglobin \= 2.0 mg/dL, or * Hypercalcemia: Ca \>= 10.5 mg/dL, or * Lytic bone lesions on X-ray, CT, or PET/CT, or * \>= 2 focal lesions on spinal MRI, or * \>= 60% bone marrow plasma cells, or * Involved/un-involved serum free light chain ration \>= 100 * Participants must have measurable disease defined by any one of the following: * Monoclonal bone marrow plasma cells \> 5% * Serum monoclonal protein \>= 0.2 g/dl * Urine monoclonal protein \> 200 mg/24 hr * Serum immunoglobulin free light chain \> 10 mg/dL AND abnormal kappa/lambda ratio * A measurable lesion on PET/CT or MRI * Participants fit criteria for one of the following categories: * Newly diagnosed multiple myeloma (NDMM) * Relapsed and/or refractory multiple myeloma (RRMM) with at least 1 prior line of therapy * Age \>=18 years. * ECOG performance status \