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

描述（由申请人提供）：目前，在前列腺癌的再分期中没有明确的成像技术。本研究的长期目标是确定合成L-亮氨酸类似物正电子发射断层扫描（PET）放射性示踪剂antf-[18 F]FACBC的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中的摄取机制。拟议研究背后的具体假设是，与标准常规成像相比，anft-[18F]FACBC PET-CT将检测到更多的局部和前列腺外复发，特别是与111铟-己内酰胺-pendetide相比。该假设部分基于体外和体内研究，这些研究证明了在人DU 145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，炎症细胞中的低蓄积，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。该建议的实验重点是anf/-[18F]FACBC检测复发性前列腺癌和区分前列腺与前列腺外复发的能力。该提案的具体目标是：目标1。研究anfr-[18F]FACBC PET-CT成像检测前列腺癌局部复发的能力。目标2.研究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antt-[18F]FACBC PET-CT成像与常规成像区分前列腺癌局部复发与前列腺外复发的能力。我们将对160名接受过前列腺癌确定性治疗并根据PSA升高怀疑复发的患者进行临床试验。我们将比较anf/-[18F]FACBC PET-CT成像与常规成像，特别是111铟-己内酰胺-pendetide在检测局部和远处癌症复发方面的能力。此外，我们计划开发试点数据（子目标1），通过RT-PCR分析研究在#-[18 F]FACBC亲合性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（子目标2）。我们认为，PET-CT与antf-[18F]FACBC成像有可能作为一种重要的非侵入性成像技术，在前列腺癌的分期和再分期，并可能监测治疗。实现本提案中的具体目标将使我们能够通过确定anf/-[18F]FACBC在评估局部复发性疾病中是否有效来评估这些可能性（具体目标#1）和前列腺外疾病（具体目标#2），区分前列腺与前列腺外复发（具体目标#3），并确定哪种LAT转运蛋白（子目标#1）和信号传导途径（子目标#2）负责anft '-[18 F]FACBC摄取。

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.