Currently, there is no definitive imaging technique in the restaging of prostate carcinoma. The long term goal of this research is to determine if PET imaging with the synthetic L-leucine analog positron emission tomography (PET) radiotracer antf-[18F]FACBC will lead to improved patient care in the diagnosis and staging of prostate cancer and to elucidate the mechanism of its uptake within malignant cells. The specific hypothesis behind the proposed research is that anft-[18F]FACBC PET-CT will detect more local and extraprostatic recurrence than standard conventional imaging, especially compared with 111lndium- capromab-pendetide. This hypothesis is based in part on in-vitro and in-vivo studies demonstrating excellent uptake within human DU145 prostate cancer cell lines and within orthotopic implanted prostate tumor in nude rats, evidence of """"""""L"""""""" type transport (LAT), low accumulation in inflammatory cells, and work in humans demonstrating excellent visualization of primary and metastatic disease. The experimental focus of this proposal is on the ability of anf/-[18F]FACBC to detect recurrent prostate carcinoma and to discriminate prostatic from extra-prostatic recurrence.
The specific aims of the proposal are:
Aim 1. Investigate the ability of anfr-[18F]FACBC PET-CT imaging to detect local recurrence of prostate cancer.
Aim 2. Investigate the ability of anft-[18F]FACBC PET-CT imaging to detect extra-prostatic recurrence of prostate cancer.
Aim 3. Compare the ability of antt-[18F]FACBC PET-CT imaging to that of conventional imaging in the discrimination of local recurrence of prostate carcinoma from that of extra-prostatic recurrence. We will undertake a clinical trial with 160 patients who have undergone definitive therapy for prostate carcinoma and who have suspected recurrence based on elevated PSA. We will compare the ability of anf/-[18F]FACBC PET-CT imaging to conventional imaging especially 111lndium-capromab-pendetide in the detection of recurrence of carcinoma both locally and distantly. In addition we plan to develop pilot data (Sub-aim 1) investigating via RT-PCR analysis which LAT gene subtypes are present in an#-[18F]FACBC avid prostate tissue. We will then utilize publicly available microarray datasets to determine which signaling pathway controls the expression of the expressed LAT subtype in tumors (Sub-aim 2). We believe PET-CT imaging with antf-[18F]FACBC has the potential to serve as an important non-invasive imaging technique in the staging and restaging of prostate carcinoma and possibly to monitor therapy. Accomplishing the specific aims in this proposal will enable us to assess these possibilities by determining if anf/-[18F]FACBC is effective in the evaluation of locally recurrent disease (Specific Aim #1) and extraprostatic disease (Specific Aim #2), discriminate between prostatic versus extraprostatic recurrence (Specific Aim #3), and determine which LAT transporter (Sub-aim #1) and signaling pathway (Sub-aim #2) are responsible for anft'-[18F]FACBC uptake.
