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

前列腺癌（PCa）是癌症相关疾病的主要原因。对于局限性疾病和预期寿命较长的男性，手术和放疗是治疗方式的选择。根治性前列腺切除术的目标是完全根除癌症，同时保留控制和效力。目前外科医生没有可靠和准确的工具来术中检测癌症，这就是为什么标准的护理仍然是目视检查和触诊以及对切除标本进行有针对性的冷冻切片分析。最近，前列腺特异性膜抗原配体（PSMA）正电子发射断层扫描（PET）已成为一种准确的检测前列腺癌的工具，无论是在原发性分期还是在生化复发时。有趣的是，PET显像剂也通过一种叫做切伦科夫发光的现象发射光子。这使得称为切伦科夫发光成像（CLI）的光学成像成为可能。由于发射的光子只能穿透约1mm厚度的上覆组织，因此CLI仅限于检测浅表前列腺癌细胞。同样，一种用于术中肿瘤切除边缘评估的新型放射自显影成像（ARI）技术最近被描述为与氟化PET示踪剂一起使用。术中放射指导可以帮助外科医生发现囊外延伸、手术边缘阳性和淋巴结转移，目的是提高手术精度，并可能改善肿瘤预后。我们项目的目的是评估CLI和ARI在前列腺癌手术中的可行性和准确性。首先，3D打印前列腺模型的体外研究将评估68ga标记或18f标记的PET剂（PSMA-11和PSMA-1007）对CLI和ARI的穿透深度和分辨率。接下来，我们将采用跨学科的方法整合影像学和病理学数据，以评估两种psma示踪剂在PCa手术中的术中分子成像。在知情同意后，患有前列腺癌和手术边缘或淋巴结转移高风险的男性（cT3期或ISUP Gleason分级4/5组或PSA >15 ng/ml）将在手术当天接受带有68ga标记的PSMA-11或18f标记的PSMA-1007的PSMA-PET/CT检查。随后，将进行根治性前列腺切除术，切除的标本将立即在体外用CLI和ARI成像，以确定肿瘤囊外延伸和手术边缘阳性的危险区域。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验证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.