Emory Molecular and Translational Imaging Center

描述（由申请人提供）：目前，没有明确的成像技术用于前列腺癌分期，特别是局部或T分期。然而，我们已经证明了使用抗-[18 F]-[18 F]-FACBC（一种合成的L-亮氨酸类似物正电子发射断层扫描（PET）放射性示踪剂）的有希望的结果。本研究的长期目标是确定PET与抗[18F] FACBC是否会改善前列腺癌诊断和分期的患者护理，并阐明其在恶性细胞内的摄取机制。第二个目标是将这项工作转化为促进使用调强放射治疗（IMRT）治疗前列腺癌。我们的第一个具体假设是前列腺内抗[18 F]FACBC的摄取将与肿瘤的存在相关，并导致原发性前列腺癌患者疾病状态的更好表征。第二个具体假设是抗[18 F] FACBC由LAT转运蛋白转运，并且可以阐明该机制和相关信号通路。我们显示了体外和体内研究，证明了在人前列腺癌细胞系内和在裸大鼠原位植入的前列腺肿瘤内的良好摄取，“L”型转运（LAT）的证据，在炎症细胞中的低积累，以及在人体中的工作，证明了原发性和转移性疾病的良好可视化。 2个主要具体目标是：目标1。将抗[18 F] FACBC的摄取与原发性前列腺癌以及局部淋巴结内的阶梯切片病理学相关联。目标二。发现哪些LAT基因亚型存在于抗[18 F] FACBC亲合性前列腺肿瘤中并表达，以及哪些信号通路控制其表达。我们将对48名计划接受前列腺切除术的患者进行一项试验，这些患者经活检证实为局限性前列腺癌。最后，在我们的次要目标中，我们将探索利用抗[18 F] FACBC摄取与前列腺解剖MRI图像融合来计划IMRT的可行性。我们相信PET-CT显像与抗-[18F] FACBC有潜力作为一个重要的非侵入性成像技术在前列腺癌分期。 实现该提议的具体目标将使我们能够通过确定抗[18 F] FACBC是否有效评估原发性前列腺癌来评估这些可能性（目标1），以确定哪些[AT转运蛋白和信号传导途径负责抗[18 F]FACBC摄取（目标2），并检查PET-MRI融合的可行性，目的是了解这是否有助于计划前列腺的IMRT（次要目标1）。

DESCRIPTION (provided by applicant): Currently, there is no definitive imaging technique for staging prostate carcinoma, especially that of local or T-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 to improved patient care in the diagnosis and staging of prostate carcinoma and to elucidate the mechanism of its uptake within malignant cells. A secondary goal is to translate this work to facilitate the use of intensity-modulated-radiation-therapy (IMRT) for treatment of prostate carcinoma. Our first specific hypothesis is that uptake of anti-[18F]FACBC within prostate will correlate to presence of tumor and lead to better characterization of disease status in primary prostate cancer patients. The second specific hypothesis is that anti-[18F] FACBC is transported by a LAT transporter and that this mechanism and related signaling pathways can be elucidated. We show in vitro and in vivo studies demonstrating excellent uptake within human prostate carcinoma 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 2 primary specific aims are: Aim 1. To correlate the uptake of anti-[18F] FACBC with step section pathology in primary prostate cancer as well as within locoregional lymph nodes. Aim 2. To discover which LAT gene subtypes are present and expressed in anti-[18F] FACBC avid prostate tumors and which signaling pathways control their expression. We will undertake a trial with 48 patients who are scheduled to 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 MRI images of the prostate to plan IMRT. We believe PET-CT imaging with anti-[18F] FACBC has the potential to 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 by determining if anti-[18F] FACBC is effective in the evaluation of primary prostatic cancer (aim 1), to determine which [AT 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 be helpful in planning IMRT to the prostate (secondary-aim 1).