This study investigates if a new drug (PSMA) makes prostate cancer easier to identify in positron-emission tomography (PET) imaging. If this works, prostate cancer treatments can be prescribed that match the location of the disease. PSMA is radiolabeled with Gallium-68 (Ga-68). This means a participant receives a small dose of radiation from the drug - less than the annual radiation limit for a medical worker.

To test this new drug, participants will receive an injection of Ga-68 PSMA and then have a PET scan. This PET scan, and the reported results, will be entered into the medical record and shared with the treating oncologists.

This study evaluates PSMA-HBED-CC labelled with Gallium-68, abbreviated 68Ga PSMA. This is a radiotracer that attaches to receptors in the membrane of prostate cancer cells. The 68Ga PSMA is identified using a positron emission tomography (PET) scanner. It is believed that 68Ga PSMA will identify prostate cancer more precisely than normal imaging methods (MRI, CT, or ultrasound). Imaging is key to successful treatment - disease must be identified to be treated.

The 68Ga PSMA will be tested in men who have biochemical recurrence of prostate cancer after surgery or radiation treatment. Participants undergo the 68Ga PSMA PET scan before further treatment. Clinical information, including any MRI, CT, or ultrasound imaging and biopsy/surgery information, will be used to determine if the 68Ga PSMA PET imaging was better than the standard imaging. The study team will collect this information for about 1 year after the PSMA scan.

Depending on findings, participants may be invited back for a second 68Ga PSMA scan. This is done if the first scan showed positive lymph nodes or soft tissue metastases but a surgery or biopsy result does not.

The results from these scans will be shared with the participant. Results will also be entered into the participant's medical record and shared with the treating oncologists.

Inclusion Criteria:

• Ability to understand and willingness to provide informed consent.
• Pathologically proven prostate adenocarcinoma.
• Rising PSA after definitive therapy with a prostatectomy or radiation therapy (external beam radiation therapy or brachytherapy).
• If post-radical prostatectomy, a PSA level of > 0.2 ng/mL measured more than 6 weeks post-operatively with a second confirmatory persistent PSA > 0.2 ng/mL.
• If post-radiation therapy, a PSA level that is equal to, or greater than, a 2 mg/mL rise above the lowest PSA value ('nadir').
• A PSA level result within the last 2 months meeting criteria above.
• Not receiving any other investigational agents (i.e., unlabeled drugs or drugs under an IND for initial efficacy investigations).
• No other malignancy within the past 2 years (skin basal cell or cutaneous superficial squamous cell carcinoma or superficial bladder cancer are exempt from this criterion).
• Karnofsky performance status greater than or equal to 50 (ECOG/WHO 0, 1, or 2) within the last 3 months.

Exclusion Criteria:

• Cannot receive furosemide.
• History of Stevens-Johnson syndrome.
• History or diagnosis of Paget's disease.
• Malignancy other than current disease under study.
• Allergy to sulfa or sulfa-containing medications.
• 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.

Codified data will be archived and stored in an imaging repository with limited metadata for analysis. A data sharing contract for a HIPAA limited dataset will need to be executed prior to data sharing.

Reviewed upon request; may not be immediately available depending upon accrual and study's completion status. Data will be archived for research purposes.

Individuals seeking use of these data should contact the study chair. A contract may be necessary for data sharing.