Prostate Specific Membrane Antigen (PMSA)-Based PET Imaging of High Risk Prostate Cancer

* INCLUSION CRITERIA:
* Patients must have histologically proven prostate adenocarcinoma confirmed by a CLIA certified laboratory.
* Must have prostate cancer with high risk features defined as:

  * Gleason 8 and higher OR
  * PSA \> 20 ng/mL OR
  * Clinical stage T3a (i.e. likely extraprostatic extension on MRI) or T3b
* Patients must be eligible for and must be planning to undergo radical prostatectomy and lymphadenectomy regardless of findings on 18F-DCFPyL PET/CT
* Men age greater than or equal to 18 years.
* ECOG performance status \<2
* Patients must have adequate organ and marrow function as defined below:

  * Hemoglobin greater than or equal to 9 g/dL
  * leukocytes greater than or equal to 3,000/mcL
  * platelets greater than or equal to 100,000/mcL
  * total bilirubin \<2 X normal institutional limits
* AST(SGOT)/ALT(SGPT) less than or equal to 3 X normal institutional limits
* creatinine \<2 X normal institutional limits

OR

eGFR greater than or equal to 50 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal. (calculated via the MDRD equation)

* Ability of subject to understand and the willingness to sign a written informed consent document.
* Willingness and ability to undergo biopsy of radiotracer-avid lesion if feasible.
* Willingness and ability to undergo multiparametric prostate MRI and 18F-DCFPyL PET/CT

EXCLUSION CRITERIA:

* Any investigational agents in the past 28 days prior to enrollment.
* Clinical stage T4 (tumor invades adjacent structures except seminal vesicles).
* Distant metastatic disease on conventional imaging studies (computed tomography (CT)) of the abdomen and pelvis and bone scan. NaF PET/CT scan cannot substitute for a bone scan. Given lack of specificity of CT for lymph node metastases at lower thresholds, pelvic lymph nodes below 2 cm in the short axis are allowed.
* Any prior hormone therapy used to treat prostate cancer, except limited androgen receptor antagonist therapy, defined as less than or equal to 3 days of treatment. The medication must be discontinued within 5 half-lives of the compound prior to study entry.
* Any prior therapy for prostate cancer with surgery, radiation, and/or chemotherapy.
* Contraindication to MRI or PET:

  * Patients weighing more than weight limit for the scanner tables or unable to fit within the imaging gantry
  * Prior reaction to 18F-DCFPyL
  * Patients with pacemakers, cerebral aneurysm clips, shrapnel injury or implantable electronic device that are not MRI compatible at 3 T
  * Severe claustrophobia unresponsive to oral anxiolytics
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Other medical conditions deemed by the principal investigator (or associates) to make the subject unsafe/ineligible for the protocol procedures or for radical prostatectomy.
* A malignancy within the past 3 years for which prostatectomy is a contraindication.
* Radiotracer administered within 5 half-lives prior to the date of 18F-DCFPyL PET/CT imaging.
* PSMA-targeted imaging within 6 months with 18F-DCFPyL tracer prior to the date of 18F-DCFPyL PET/CT imaging. Participants can have PSMA targeted imaging with Gallium.
* Unable to refrain from fathering a child or donating sperm for 10 days after each 18F-DCFPyL injection.