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

目前，对于前列腺癌的分期，特别是局部前列腺癌的分期，尚无明确的影像技术。 或登台表演。然而，我们已经展示了反1-氨基-3-[18F]氟环丁基-1- 羧酸(抗[18F]FACBC)，合成的L亮氨酸类似物正电子发射断层扫描 放射性示踪剂。这项研究的长期目标是确定带有抗[18F]FACBC的PET是否会导致 改进前列腺癌的诊断和分期并阐明其机制的护理 它在恶性肿瘤细胞中的摄取。第二个目标是翻译这部作品，以便于使用 调强放射治疗(IMRT)治疗前列腺癌我们的第一个特别节目 假设前列腺内摄取抗[18F]FACBC将与肿瘤和铅的存在相关 为了更好地描述原发性前列腺癌患者的疾病状况。第二个具体问题 假设抗[18F]FACBC是由LAT转运体运输的，这一机制和 相关的信号通路可以被阐明。我们展示了体外和体内研究证明 人前列腺癌细胞系和原位移植前列腺内的良好摄取 裸鼠肿瘤，“L”型转移的证据，炎性细胞的低聚集，以及功 在表现出对原发和转移疾病的良好可视化的人类中 主要的两个具体目标是：目标1.将抗[18F]FACBC的摄取与STEP切片相关联 原发性前列腺癌以及局部区域淋巴结内的病理学。目标2.发现 在抗[18F]FACBC的良性前列腺肿瘤中存在和表达哪些LAT基因亚型 信号通路控制着它们的表达。我们将对48名预定的患者进行试验 对活检证实的局限性前列腺癌进行前列腺切除术。最后在我们的次要目标中， 我们将探索利用融合到解剖MRI中的抗[18F]FACBC摄取的可行性 前列腺图像以计划调强放射治疗。我们相信使用抗[18F]FACBC的PET-CT成像具有潜力 可作为前列腺癌分期的重要无创性影像检查方法。 实现该提案的具体目标将使我们能够通过以下方式评估这些可能性 确定抗[18F]FACBC在评估原发性前列腺癌中是否有效(目标1)，以 确定哪些LAT转运体和信号通路负责抗[18F]FACBC摄取 (目标2)，并研究PET-MRI融合的可行性，目的是了解这是否可能 有助于计划对前列腺进行调强放射治疗(次级目标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)