The purpose of this study is to see if using Positron Emission Tomography (PET) scan and transrectal ultrasound (TRUS) guided biopsy together (creating a 3-dimensional ultrasound) will detect prostate cancer more accurately than the standard 2-dimensional approach which uses only the TRUS to guide the biopsy.

The objective of the proposed study is to evaluate a molecular image directed, three-dimensional (3D) ultrasound guided biopsy system in human patients. Prior studies have shown that Positron Emission Tomography (PET)/Computed Tomography (CT) imaging with the PET molecular imaging agent, a synthetic amino acid, anti-1-amino-3-[18F]fluorocyclobutane-1- carboxylic acid (FACBC), is more sensitive than the FDA-approved prostate specific membrane antigen single-photon emission computed tomography (SPECT) radiotracer in prostate cancer detection. FACBC images showed higher focal uptake in tumor foci than in normal prostate and thus could be ideal information to direct targeted biopsy of the prostate. This targeted biopsy system has a unique feature that PET/CT images can be registered with 3D ultrasound images, as a result, a suspicious PET lesion is superimposed over the real-time ultrasound data; and the fused image is then used to direct biopsy needles to tumor targets.

The hypothesis of the study is that PET/ultrasound fusion targeted biopsy can detect more cancer per core than the standard 12-core TRUS guided biopsy.

The specific aims include:

1. To perform PET/CT directed, 3D ultrasound-guided biopsy and determine if fusion targeted biopsy can detect more cancers than 2D transrectal ultrasound (TRUS)-guided biopsy
2. To develop the workflow for performing deformable registration and fusion of PET/CT and 3D ultrasound images of human patients

Thirty six patients, who have suspicion of recurrent prostate cancer after definitive therapy such as radiotherapy, will be recruited into this study. At least half of the patients will have positive imaging findings and will undergo 2D TRUS-guided biopsy as well as PET/ultrasound fusion biopsy. The proposed study will be the first-in-human trial that uses PET/CT imaging to direct 3D ultrasound-guided biopsy of the prostate. The multimodality imaging approach will combine the high sensitivity from PET and real-time information from ultrasound for improved cancer detection.

Inclusion Criteria:

• Have been originally diagnosed with prostate carcinoma and have undergone definitive non-prostatectomy therapy for localized disease
• There is suspicion of recurrent prostate carcinoma as defined by: Older American Society for Radiation Oncology (ASTRO) criteria of three consecutive rises of prostate-specific antigen (PSA) or earlier if clinically appropriate, and/or nadir + 2.0 ng/ml (Radiation Therapy Oncology Group (RTOG)-ASTRO Phoenix criteria)
• Able to provide written informed consent

Exclusion Criteria:

• Cryotherapy, external beam radiation, or high intensity focused ultrasound (HIFU) within the past year
• Brachytherapy within the past two years (to rule out a transient rise in PSA)
• Prostate biopsy within the past month (to decrease a false positive result due to inflammation)
• Not otherwise eligible for prostate biopsy

The time period for collecting adverse events was from the the time of the FACBC PET-CT scan until 7 days after the scan. Since 95% of the ligand used during the scan is eliminated within 7 days, any events beyond 7 days after the scan were not considered to be adverse events due to study procedures.

This study only collected adverse events that were a significant shift from baseline and which could be attributed to the radiotracer injection and not the patient's prior medical condition. No adverse events due to the study procedures were anticipated.