Molecular Imaging with FACBC PET-CT to Improve Post prostatectomy Radiotherapy

描述(申请人提供)：我们的总体目标是通过改变现有的决策算法，通过先进的分子成像能力来指导适当选择将从挽救放射治疗中受益的患者，从而提高复发前列腺癌患者的长期无生化生存。在前列腺特异性抗原(PSA)失效或活检证实前列腺床复发后接受前列腺术后放射治疗的患者中，大约50%的患者随后出现全身疾病，部分原因是传统的成像方法无法充分区分前列腺癌和前列腺外复发。在前列腺切除术后的环境中，根据现有的策略，治疗不足和治疗过度都会发生，在这一人群中，适当地指导放射治疗是一个未得到满足的公共卫生需求。我们计划利用先进的分子成像与正电子发射断层扫描放射示踪剂anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic酸(抗3-[18F]FACBC)，它在初步数据中能够区分前列腺癌和前列腺外复发，即使在低PSA值。这样做将能够更适当地选择将从挽救放射治疗中受益的患者，并在比先前认为的更高的PSA水平下实现持久的反应。我们假设，如果患者被适当地选择进行挽救放射治疗，借助新推出的先进分子成像和抗3-[18F]FACBC PET-CT，将有显著更高的比例实现长期治愈，并达到比传统治疗算法更高的PSA水平。我们还假设，先进分子成像的使用将改变前列腺癌切除术后放射治疗的算法，无论是在治疗的决定上还是在计划体积上。为了验证这两个假设，我们计划进行一项前瞻性随机临床试验，在对照组(A)中，患者将在常规成像方法之后接受挽救放射治疗，而在试验组(B)中，患者将接受抗3-[18F]FACBC PET-CT的治疗。我们将探讨抗3-[18F]FACBC PET-CT在以下方面的作用：(1)控制通常不能接受前列腺癌切除术后放射治疗的前列腺癌，并改善一般可考虑进行放射治疗的患者的前列腺癌控制；(2)在提供放射治疗的总体决定和引导总辐射场(前列腺床与盆腔)的决定中指导放射治疗决策；(3)在计划和实施放射治疗时影响靶区体积和正常结构的重叠。这项工作将对改善前列腺切除术后患者的预后具有重要意义，不仅对于抗3-[18F]FACBC的使用，而且对于应用新的成像来指导前列腺切除术后放射治疗具有重要意义。 公共卫生相关性：先进的分子成像和抗3-[18F]FACBC PET-CT用于改善前列腺癌患者接受前列腺癌切除术后放射治疗的选择和结果项目叙述/相关性前列腺癌治疗的失败是一个重大的健康问题。放射治疗通常在手术失败后使用，但目前用于指导放射治疗决定和治疗计划的传统成像技术相当有限。该提案的总体目标是确定先进分子成像的作用，重点放在一种特别的新型放射性示踪剂(抗3-[18F]FACBC)上，对其有重要的初步数据，在改善前列腺癌术后放射治疗患者的选择和改善前列腺癌预后方面。

DESCRIPTION (provided by applicant): Our overall goal is to improve the long term biochemical free survival of patients with recurrent prostate carcinoma by altering the current decision algorithm through the ability of advanced molecular imaging to guide the appropriate selection of patients who will benefit from salvage radiotherapy. Approximately 50% of patients who have undergone post-prostatectomy radiotherapy after Prostate Specific Antigen (PSA) failure or biopsy proven prostate bed recurrence manifest subsequent systemic disease, in part, because conventional imaging methods fail to adequately differentiate prostatic from extraprostatic recurrence. In the post-prostatectomy setting, both under-treatment and over- treatment occur based on existing strategies, and appropriately directing radiotherapy is an unmet public health need in this population. We plan to leverage advanced molecular imaging with the positron emission tomography (PET) radiotracer anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid (anti-3-[18F]FACBC) which in preliminary data is able to differentiate prostatic from extra-prostatic recurrence even at low PSA levels. Doing so will enable more appropriate selection of patients who will benefit from salvage radiotherapy and to achieve durable response at higher PSA levels than previously believed. We hypothesize that if patients are appropriately selected for salvage radiotherapy with the aid of newly available advanced molecular imaging with anti-3-[18F]FACBC PET-CT, a significantly higher proportion will achieve long-term cure and at higher PSA levels than via conventional treatment algorithms. We also hypothesize that the use of advanced molecular imaging will alter post-prostatectomy radiotherapy algorithms both in decision to treat and in planning volumes. To test these two hypothesis, we plan to conduct a prospective randomized clinical trial in which patients will be treated with salvage radiotherapy after conventional imaging methods in the control arm (A) and with the addition of anti-3-[18F]FACBC PET-CT in the trial arm (B). We will explore the role of anti-3-[18F]FACBC PET-CT in (1) controlling prostate cancer that would otherwise generally not be treated with post- prostatectomy radiotherapy, and improving prostate cancer control in patients that would generally be considered for radiotherapy, (2) guiding radiotherapy decisions, both in the overall decision to offer radiotherapy and in the decision to guide the general radiation field (prostate bed versus pelvis), and (3) influencing the target volume and overlap of normal structures when planning and delivering radiotherapy. The work will have significant implications for improving the outcomes of post-prostatectomy patients, not just for the use of anti-3-[18F]FACBC but for the application of novel imaging to guide post-prostatectomy radiotherapy. PUBLIC HEALTH RELEVANCE: Advanced Molecular Imaging with anti-3-[18F]FACBC PET-CT to Improve the Selection and Outcomes of Prostate Cancer Patients Receiving Post-prostatectomy Radiotherapy Project Narrative/Relevance Failure of prostate cancer treatment is a significant health problem. Radiotherapy is often used after surgical failures, but the conventional imaging techniques currently used to guide radiotherapy decisions and treatment planning are quite limited. The overall goal of the proposal establish the role of advanced molecular imaging, with focus on one particular novel radiotracer (anti-3-[18F]FACBC) for which there is significant preliminary data, in improving the selection of patients for post-prostatectom radiotherapy and in improving prostate cancer outcomes.