Evaluating the feasibility and accuracy of novel intra-operative molecular imaging with two PSMA-tracers in prostate cancer surgery

前列腺癌（PCa）是癌症相关发病率的主要原因。在局部疾病和预期寿命长的男性中，手术和放射治疗是首选的治疗方式。根治性乳腺癌切除术的目标是完全根除癌症，同时保留乳房和潜力。目前，外科医生没有可靠和准确的工具来术中检测癌症，这就是为什么护理标准仍然是目视检查和触诊以及切除标本的靶向冷冻切片分析。最近，前列腺特异性膜抗原配体（PSMA）正电子发射断层扫描（PET）已成为一种准确的工具，以检测PCa在原发分期和生化复发的时间。有趣的是，PET成像剂还通过称为切伦科夫发光的现象发射可见光子。这使得能够进行称为切伦科夫发光成像（CLI）的光学成像。由于发射的光子仅穿透约1 mm厚的覆盖组织，因此CLI仅限于检测浅表前列腺癌细胞。类似地，最近描述了一种用于术中评价肿瘤切除边缘的新型放射自显影成像（ARI）技术，用于氟化PET示踪剂。术中放射性引导可以帮助外科医生检测囊外扩张、阳性手术切缘和淋巴结转移，目的是提高手术精度并可能改善肿瘤学结局。我们的项目的目的是评估CLI和ARI在前列腺癌手术中的新成像的可行性和准确性。首先，使用3D打印前列腺模型的体外研究将评估68 Ga标记或18F标记的PET试剂（PSMA-11和PSMA-1007）的CLI和ARI的渗透深度和分辨率。接下来，我们将使用一个跨学科的方法整合成像和病理数据，以评估术中分子成像与两个PSMA示踪剂在PCa手术。在知情同意后，具有PCa和阳性手术切缘或淋巴结转移的高风险（cT 3阶段或ISUP Gleason分级组4/5或PSA >15 ng/ml）的男性将在手术当天用68 Ga标记的PSMA-11或18 F标记的PSMA-1007进行PSMA-PET/CT。随后，将进行根治性直肠癌切除术，并立即使用CLI和ARI对切除的标本进行离体成像，以确定存在癌症囊外扩散风险的区域和阳性手术切缘。如果这项评估CLI和ARI的可行性和准确性的研究显示出益处，那么更大规模的研究将测试这种方法可以改善局部癌症控制的假设。

Prostate cancer (PCa) is a leading cause of cancer-related morbidity. In men with localized disease and a long life expectancy surgery and radiotherapy are the treatment modalities of choice. The goal of radical prostatectomy is complete eradication of cancer while preserving continence and potency. Currently surgeons have no reliable and accurate tool to intra-operatively detect cancer, which is why standard of care remains visual inspection and palpation as well as targeted frozen section analysis of excised specimen. Recently, prostate-specific membrane antigen ligand (PSMA) positron emission tomography (PET) has emerged as an accurate tool to detect PCa in both primary staging and at time of biochemical recurrence. Interestingly, PET imaging agents also emit optical photons via a phenomenon called Cerenkov luminescence. This enables optical imaging called Cerenkov Luminescence Imaging (CLI). Because the emitted photons only penetrate overlying tissues of approximately 1 mm thickness CLI is limited to detection of superficial prostate cancer cells. Similarly, a novel autoradiography imaging (ARI) technique for intraoperative evaluation of tumor resection margins has been described lately for use with fluorinated PET tracers. Intraoperative radioguidance may help surgeons in the detection of extracapsular extension, positive surgical margins and lymph node metastases with the aim of increasing surgical precision and possibly improving oncological outcome.The objective of our project is to assess the feasibility and accuracy of novel imaging with CLI and ARI in prostate cancer surgery. First, in vitro studies with 3D printed prostate models will evaluate penetration depth and resolution of CLI and ARI with 68Ga-labelled or 18F-labelled PET agents (PSMA-11 and PSMA-1007). Next, we will use an interdisciplinary approach integrating imaging and pathological data in order to evaluate intra-operative molecular imaging with the two PSMA-tracers in PCa surgery. After informed consent, men with PCa and a high risk of positive surgical margins or lymph node metastases (cT3 stage or ISUP Gleason grade group 4/5 or PSA >15 ng/ml) will undergo PSMA-PET/CT with 68Ga-labelled PSMA-11 or 18F-labelled PSMA-1007 on the day of surgery. Subsequently, radical prostatectomy will be performed and excised specimen will be imaged immediately ex vivo with CLI and ARI in order to identify regions at risk for extracapsular extension of cancer and positive surgical margins. If this study assessing feasibility and accuracy of CLI and ARI shows benefit, larger studies will test the hypothesis that local cancer control can be improved by this approach.