Emory Molecular and Translational Imaging Center

描述(申请人提供)：目前，对于前列腺癌的分期，特别是局部或T分期，尚无明确的影像技术。然而，我们已经证明了反1-氨基-3-[18F]氟环丁基-1-羧酸(反[18F]FACBC)，一种合成的L-亮氨酸类似的正电子发射断层扫描(PET)放射性示踪剂的良好结果。这项研究的长期目标是确定使用抗[18F]FACBC的PET是否会改善前列腺癌的诊断和分期中的患者护理，并阐明其在恶性细胞内摄取的机制。第二个目标是翻译这项工作，以促进使用调强放射治疗(IMRT)治疗前列腺癌。我们的第一个特定假设是，前列腺内摄取抗[18F]FACBC将与肿瘤的存在相关，并导致更好地描述原发性前列腺癌患者的疾病状况。第二个具体的假设是，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。我们的体外和体内研究表明，在人前列腺癌细胞系和裸鼠原位移植的前列腺癌中有很好的摄取，“L”型转运(LAT)的证据，炎性细胞的低聚集，以及在人类身上的工作证明了对原发和转移疾病的良好可视化。 两个主要的特异性目标是：目的1.研究原发性前列腺癌和局部区域淋巴结中抗[18F]FACBC的摄取与分级切片病理的相关性。目的2.探讨LAT基因在抗[18F]FACBC的前列腺癌中存在和表达的亚型，以及哪些信号通路控制其表达。我们将对48名计划接受前列腺癌切除术的患者进行试验，这些患者经活检证实为局限性前列腺癌。最后，在我们的第二个目标中，我们将探索利用融合到前列腺解剖MRI图像的抗[18F]FACBC摄取来计划IMRT的可行性。我们相信抗[18F]FACBC的PET-CT成像有可能成为前列腺癌分期的一种重要的非侵入性成像技术。 通过确定抗[18F]FACBC在评估原发性前列腺癌中是否有效(目标1)，确定哪些[AT转运体和信号通路]负责抗[18F]FACBC摄取(目标2)，以及检查PET-MRI融合的可行性，目的是了解这是否有助于计划前列腺IMRT(次级目标1)，从而评估这些可能性。

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).