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

18F-FACBC PET-CT 用于复发性前列腺癌的检测和分期

• 批准号: 7661484
• 负责人: David Michael Schuster
• 金额: $ 34.4万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-21 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7661484
• 关键词: Affect; Age; Amino Acid Transporter; Ants; Beds; Bioinformatics; Biopsy; Capromab Pendetide; Carboxylic Acids; Carcinoma; Cells; Clinical; Clinical Trials; DU145; Data; Data Set; Detection; Diagnosis; Discrimination; Disease; Evaluation; Excision; Extraprostatic; Genes; Goals; Human; Image; Imagery; Imaging Techniques; Implant; In Vitro; Incidence; Inflammatory; Investigation; Lasers; Lead; Leucine; Lymphadenitis; Malignant neoplasm of prostate; Meta-Analysis; Metastatic Prostate Cancer; Methods; Mining; Modeling; Monitor; Mus; Nodal; Nude Rats; PC3 cell line; Pathologic; Pathway interactions; Patient Care; Patients; Pharmaceutical Preparations; Population; Positron-Emission Tomography; Prostate; Prostate carcinoma; Prostate-Specific Antigen; Prostatic; Prostatic Neoplasms; Proteins; Recurrence; Recurrent disease; Research; Research Personnel; Reverse Transcriptase Polymerase Chain Reaction; SLC43A1 gene; Sampling; Screening procedure; Signal Pathway; Signal Transduction Pathway; Skeletal system; Staging; Structure; Study Section; Tissue Sample; Tissues; Transrectal Ultrasound; Work; analog; base; cancer cell; design; follow-up; improved; in vivo; lymph nodes; neoplastic cell; programs; radiotracer; receptor expression; tool; transport inhibitor; tumor; tumor progression; uptake

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.

描述（由申请人提供）：目前，前列腺癌的再分期尚无明确的成像技术。本研究的长期目标是确定使用合成 L-亮氨酸模拟正电子发射断层扫描 (PET) 放射性示踪剂 antf-[18F]FACBC 进行 PET 成像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的摄取机制。拟议研究背后的具体假设是，与标准传统成像相比，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 111Indium-capromab-pendetide 相比。该假设部分基于体外和体内研究，证明在人 DU145 前列腺癌细胞系和裸鼠原位植入前列腺肿瘤内具有良好的摄取，“L”型转运 (LAT) 的证据，炎症中的低积累细胞，并在人体中发挥作用，展示出原发性疾病和转移性疾病的出色可视化效果。该提案的实验重点是anf/-[18F]FACBC检测复发性前列腺癌和区分前列腺癌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 成像与常规成像在区分前列腺癌局部复发和前列腺外复发方面的能力。我们将对 160 名接受过前列腺癌根治性治疗且因 PSA 升高而疑似复发的患者进行一项临床试验。我们将比较 anf/-[18F]FACBC PET-CT 成像与传统成像尤其是 111Indium-capromab-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 分析调查 #-[18F]FACBC 狂热前列腺组织中存在哪些 LAT 基因亚型。然后，我们将利用公开的微阵列数据集来确定哪个信号通路控制肿瘤中表达的 LAT 亚型的表达（子目标 2）。我们相信 antf-[18F]FACBC PET-CT 成像有潜力成为前列腺癌分期和再分期中重要的非侵入性成像技术，并可能用于监测治疗。实现本提案中的具体目标将使我们能够通过确定 anf/-[18F]FACBC 是否有效评估局部复发性疾病（具体目标 #1）和前列腺外疾病（具体目标 #2）来评估这些可能性，区分前列腺复发与前列腺外复发之间的比较（具体目标#3），并确定哪个 LAT 转运蛋白（子目标#1）和信号通路（子目标#2）负责anft'-[18F]FACBC 吸收。