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

• Applicants: Professor Dr. Boris Hadaschik; Professor Dr. Ken Herrmann
• Subject Area: Nuclear Medicine, Radiotherapy, Radiobiology ; Reproductive Medicine, Urology
• Term: from 2020 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 437635687

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.

• DFG Programme: Research Grants
• Co-Investigator: Dr. Christopher Darr