Anti-[18 F] FACBC PET-CT for Characterization of Primary Prostate Carcinoma

目前，还没有明确的成像技术用于前列腺癌的分期，特别是局部前列腺癌的分期。 或T分期。然而，我们已经证明了用抗-1-氨基-3-[18F]氟环丁基-1-（三氟甲基）-IH-吡唑-4-胺的有希望的结果。 羧酸（抗-[18F]FACBC），一种合成的L-亮氨酸类似物正电子发射断层扫描（PET） 放射性示踪剂本研究的长期目标是确定抗[18 F]FACBC的PET是否会导致 改善前列腺癌诊断和分期的患者护理，并阐明其机制 在恶性细胞中的摄取。第二个目标是翻译这项工作，以促进使用 调强放射治疗（IMRT）用于治疗前列腺癌。我们的第一个具体 假设前列腺内抗-[18 F]FACBC摄取与肿瘤和铅的存在相关 以更好地表征原发性前列腺癌患者的疾病状态。第二特定 假设抗[18 F]FACBC由LAT转运蛋白转运，并且该机制和 可以阐明相关的信号传导途径。我们展示了体外和体内研究， 在人前列腺癌细胞系内和原位植入的前列腺内的良好摄取 裸鼠肿瘤，“L”型转运（LAT）的证据，炎症细胞中的低积累，以及工作 在人类中表现出对原发性和转移性疾病的良好可视化 这两个主要的具体目标是：目标1。将抗-[18F] FACBC的摄取与阶跃截面相关联 原发性前列腺癌以及局部淋巴结内的病理学。目标2.发现 其中LAT基因亚型在抗[18 F]FACBC亲合性前列腺肿瘤中存在并表达， 信号通路控制它们的表达。我们将对48名患者进行试验， 因活检证实的局限性前列腺癌而接受前列腺切除术。最后，在我们的次要目标中， 我们将探索利用抗[18 F]FACBC摄取与解剖MRI融合的可行性 前列腺的图像来计划IMRT。我们认为PET-CT显像与抗[18F]FACBC有潜力 作为一种重要的非侵入性成像技术在前列腺癌的分期。 实现这一建议的具体目标将使我们能够评估这些可能性， 确定抗-[18F]FACBC在评估原发性前列腺癌中是否有效（目的1）， 确定哪些LAT转运蛋白和信号通路负责抗[18 F]FACBC摄取 (aim 2），并检查PET-MRI融合的可行性，目的是了解这是否可能 有助于计划前列腺调强放射治疗（次要目标1）

Currently, there is no definitive imaging technique for staging prostate carcinoma, especially that of local orT-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 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 be helpful in planning IMRT to the prostate (secondary-aim 1)