Currently, there is no definitive imaging technique for staging prostate carcinoma, especially that of localorT-staging. Yet we have demonstrated promising results with anti-1-amino-3-[18F]fluorocyclobutyl-1-carboxylic acid (anti-[18F]FACBC), a synthetic L-leucine analog positron emission tomography (PET)radiotracer. The long term goal of this research is to determine if PET with anti-[18F]FACBC will lead toimproved patient care in the diagnosis and staging of prostate carcinoma and to elucidate the mechanismof its uptake within malignant cells. A secondary goal is to translate this work to facilitate the use ofintensity-modulated-radiation-therapy (IMRT) for treatment of prostate carcinoma. Our first specifichypothesis is that uptake of anti-[18F]FACBC within prostate will correlate to presence of tumor and leadto better characterization of disease status in primary prostate cancer patients. The second specifichypothesis is that anti-[18F]FACBC is transported by a LAT transporter and that this mechanism andrelated signaling pathways can be elucidated. We show in vitro and in vivo studies demonstratingexcellent uptake within human prostate carcinoma cell lines and within orthotopic implanted prostatetumor in nude rats, evidence of 'L' type transport (LAT), low accumulation in inflammatory cells, and workin humans demonstrating excellent visualization of primary and metastatic diseaseThe 2 primary specific aims are:
Aim 1. To correlate the uptake of anti-[18F] FACBC with step sectionpathology in primary prostate cancer as well as within locoregional lymph nodes.
Aim 2. To discoverwhich LAT gene subtypes are present and expressed in anti-[18F]FACBC avid prostate tumors and whichsignaling pathways control their expression. We will undertake a trial with 48 patients who are scheduledto undergo prostatectomy for biopsy-proven confined prostate carcinoma. Finally in our secondary aim,we will explore the feasibility of exploiting the uptake of anti-[18F]FACBC with fusion to anatomic MRIimages of the prostate to plan IMRT. We believe PET-CT imaging with anti-[18F]FACBC has the potentialto serve as an important non-invasive imaging technique in the staging of prostate carcinoma.Accomplishing the specific aims of this proposal will enable us to assess these possibilities bydetermining if anti-[18F]FACBC is effective in the evaluation of primary prostatic cancer (aim 1), todetermine which LAT transporters and signaling pathways are responsible for anti-[18F]FACBC uptake(aim 2), and to examine the feasibility of PET-MRI fusion with the purpose of understanding if this may behelpful in planning IMRT to the prostate (secondary-aim 1)
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