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

描述（由申请方提供）：我们的总体目标是通过先进的分子成像技术指导适当选择将从挽救性放疗中获益的患者，从而改变当前的决策算法，提高复发性前列腺癌患者的长期无生化生存期。在前列腺特异性抗原（PSA）失败或活检证实的前列腺床复发后接受前列腺切除术后放疗的患者中，约50%表现出随后的全身性疾病，部分原因是常规成像方法无法充分区分前列腺和前列腺外复发。在子宫切除术后的环境中，基于现有策略，治疗不足和过度治疗都发生，并且适当定向放射治疗是该人群中未满足的公共卫生需求。我们计划利用正电子发射断层扫描（PET）放射性示踪剂抗1-氨基-3-[18 F]氟环丁烷-1-羧酸（抗3-[18 F]FACBC）的先进分子成像，初步数据显示，即使在低PSA水平下，也能够区分前列腺和前列腺外复发。这样做可以更适当地选择将从挽救性放疗中获益的患者，并在比以前认为的更高的PSA水平下实现持久的缓解。我们假设，如果患者在抗3-[18 F]FACBC PET-CT的新可用先进分子成像的帮助下被适当选择接受挽救性放疗，则与传统治疗算法相比，实现长期治愈和PSA水平较高的比例显著较高。我们还假设，先进的分子成像技术的使用将改变直肠癌切除术后的放射治疗算法，无论是在决定治疗和规划体积。为了检验这两个假设，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后接受补救放疗，在试验组（B）中，患者将接受抗3-[18 F]FACBC PET-CT治疗。我们将探索抗3-[18 F]FACBC PET-CT在以下方面的作用：（1）控制前列腺癌，否则通常不会用前列腺切除术后放疗治疗，并改善通常考虑放疗的患者的前列腺癌控制，（2）指导放疗决策，无论是在提供放射治疗的总体决策中，还是在指导一般放射领域的决策中，（前列腺床对骨盆），和（3）在计划和递送放射治疗时影响目标体积和正常结构的重叠。这项工作将对改善乳腺癌切除术后患者的预后具有重要意义，不仅是使用抗3-[18 F]FACBC，而且是应用新型成像技术指导乳腺癌切除术后放疗。

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.