18F-FACBC PET-CT for the Detection and Staging of Recurrent Prostate Carcinoma

描述（由申请人提供）：目前，前列腺癌的再切没有明确的成像技术。本研究的长期目标是确定使用合成l -亮氨酸类似物正电子发射断层扫描（PET）放射性示踪剂anti -[18F]FACBC进行PET成像是否会改善前列腺癌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。提出的研究背后的具体假设是，与标准常规成像相比，anft-[18F]FACBC PET-CT能发现更多的局部和前列腺外复发，特别是与111lndium- campromab - penddetide相比。这一假设部分基于体外和体内研究，这些研究表明，人DU145前列腺癌细胞系和裸鼠原位植入前列腺肿瘤具有良好的摄取，“L”型转运（LAT）的证据，炎症细胞的低积聚，以及在人体内的工作表明，原发性和转移性疾病具有良好的可视化效果。本课题的实验重点是研究anf/-[18F]FACBC检测复发性前列腺癌以及区分前列腺癌和前列腺外复发的能力。该建议的具体目标是：目标1。探讨anfr-[18F]FACBC PET-CT成像检测前列腺癌局部复发的能力。目标2。探讨anft-[18F]FACBC PET-CT成像检测前列腺癌前列腺外复发的能力。目标3。比较anti -[18F]FACBC PET-CT显像与常规显像鉴别前列腺癌局部复发与前列腺外复发的能力。我们将进行一项临床试验，160名患者接受了前列腺癌的最终治疗，并根据PSA升高怀疑复发。我们将比较anf/-[18F]FACBC PET-CT成像与常规成像，特别是111au - campromab -pendetide在局部和远处检测癌复发的能力。此外，我们计划开发试点数据（Sub-aim 1），通过RT-PCR分析研究在#-[18F]FACBC前列腺组织中存在哪些LAT基因亚型。然后，我们将利用公开可用的微阵列数据集来确定哪种信号通路控制肿瘤中表达的LAT亚型的表达（Sub-aim 2）。我们认为，使用抗f-[18F]FACBC进行PET-CT成像有可能成为前列腺癌分期和再分期的重要非侵入性成像技术，并可能用于监测治疗。完成本提案的具体目标将使我们能够通过确定anf/-[18F]FACBC是否有效评估局部复发性疾病（specific Aim #1）和前列腺外疾病（specific Aim #2），区分前列腺和前列腺外复发（specific Aim #3），以及确定哪种LAT转运蛋白（Sub-aim #1）和信号通路（Sub-aim #2）负责anf '-[18F]FACBC摄取来评估这些可能性。

DESCRIPTION (provided by applicant): Currently, there is no definitive imaging technique in the restaging of prostate carcinoma. The long term goal of this research is to determine if PET imaging with the synthetic L-leucine analog positron emission tomography (PET) radiotracer antf-[18F]FACBC will lead to improved patient care in the diagnosis and staging of prostate cancer and to elucidate the mechanism of its uptake within malignant cells. The specific hypothesis behind the proposed research is that anft-[18F]FACBC PET-CT will detect more local and extraprostatic recurrence than standard conventional imaging, especially compared with 111lndium- capromab-pendetide. This hypothesis is based in part on in-vitro and in-vivo studies demonstrating excellent uptake within human DU145 prostate cancer 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 experimental focus of this proposal is on the ability of anf/-[18F]FACBC to detect recurrent prostate carcinoma and to discriminate prostatic from extra-prostatic recurrence. The specific aims of the proposal are: Aim 1. Investigate the ability of anfr-[18F]FACBC PET-CT imaging to detect local recurrence of prostate cancer. Aim 2. Investigate the ability of anft-[18F]FACBC PET-CT imaging to detect extra-prostatic recurrence of prostate cancer. Aim 3. Compare the ability of antt-[18F]FACBC PET-CT imaging to that of conventional imaging in the discrimination of local recurrence of prostate carcinoma from that of extra-prostatic recurrence. We will undertake a clinical trial with 160 patients who have undergone definitive therapy for prostate carcinoma and who have suspected recurrence based on elevated PSA. We will compare the ability of anf/-[18F]FACBC PET-CT imaging to conventional imaging especially 111lndium-capromab-pendetide in the detection of recurrence of carcinoma both locally and distantly. In addition we plan to develop pilot data (Sub-aim 1) investigating via RT-PCR analysis which LAT gene subtypes are present in an#-[18F]FACBC avid prostate tissue. We will then utilize publicly available microarray datasets to determine which signaling pathway controls the expression of the expressed LAT subtype in tumors (Sub-aim 2). We believe PET-CT imaging with antf-[18F]FACBC has the potential to serve as an important non-invasive imaging technique in the staging and restaging of prostate carcinoma and possibly to monitor therapy. Accomplishing the specific aims in this proposal will enable us to assess these possibilities by determining if anf/-[18F]FACBC is effective in the evaluation of locally recurrent disease (Specific Aim #1) and extraprostatic disease (Specific Aim #2), discriminate between prostatic versus extraprostatic recurrence (Specific Aim #3), and determine which LAT transporter (Sub-aim #1) and signaling pathway (Sub-aim #2) are responsible for anft'-[18F]FACBC uptake.