Background: Conventional imaging of prostate cancer has limitations in staging, restaging after biochemical relapse, and response assessment. Functional imaging with positron emission tomography (PET) can target various aspects of tumor biology and has shown to be superior in the detection of prostate cancer compared with conventional computed tomography (CT) and bone scans. 18F-Fluciclovine, a synthetic amino acid transported across mammalian cell membranes by amino acid transporters that is upregulated to a greater extent in prostate cancer cells than in surrounding tissue, is currently approved for PET imaging for patients with biochemical recurrence. The role of 18F-Fluciclovine PET scans in monitoring response to novel hormonal therapies such as abiraterone acetate is unclear. We hypothesize that 1) using 18F-Fluciclovine PET scanning will allow a more sensitive assessment of mCRPC patients at the initiation of systemic therapy with abiraterone acetate and 2) the changes observed in 18F-Fluciclovine PET will correlate better with the serologic changes in PSA, allowing superior disease monitoring, than conventional imaging modalities. Methods: This single-arm, pilot study (NCT04158245) will describe the changes in 18F-Fluciclovine PET scan and compare these results with PSA and conventional computerized tomography (CT) and bone scans, in mCRPC patients treated with abiraterone acetate plus prednisone. Patients must have a detectable baseline PSA of ≥ 2 ng/mL and metastatic disease detected on conventional CT and bone scans. The use of docetaxel in the hormone-sensitive setting is allowed. Twelve patients will be treated with abiraterone 1000 mg daily plus prednisone 5 mg (or dexamethasone 0.5 mg) daily for mCRPC and get 18F-Fluciclovine PET and conventional CT and bone scans at baseline and 12 weeks after starting abiraterone therapy or at disease progression. PSA progression will be defined as a repeated increase in PSA of at least 2 ng/dL and 25% from nadir values, at least 1 week apart, according to PCWG3 criteria and clinical or radiographic progression by RECIST version 1.1. The co-primary objectives of the study include the 18F-Fluciclovine PET changes at baseline and 12 weeks after abiraterone acetate for mCRPC and the comparison between 18F-Fluciclovine PET and conventional scans. Secondary and exploratory endpoints include PSA response, PSA progression and genomic alterations by next-generation sequencing. As of 12 September 2020, this trial is actively enrolling. Clinical trial information: NCT04158245