A new light on prostate cancer

Abstract

Ga-PSMA-11 as intraoperative margin assessment technology in prostate cancer surgery. This research includes both the pre-clinical in vitro performance evaluation of the technique, as well as a clinical feasibility trial. In addition, repeatability of the 68 Ga-PSMA-11 PET/CT in both static and dynamic PET acquisitions was investigated to determine uptake patterns and usability of preoperative 68 Ga-PSMA-11 PET/CT in the CLI workflow.Part I of this thesis focusses on the application of and requirements for intraoperative margin assessment techniques in prostate cancer surgery. Chapter 2 is a systematic review of the different options for intraoperative margin assessment in the operating room. The technical background of different methods is provided, the application in prostate cancer surgery, and the advantages and drawbacks for clinical implementation. Prior to investigating the feasibility of intraoperative margin assessment using CLI, the performance of 68 Ga-PSMA-11 for CLI needs to be evaluated. So far, CLI is only used with 18 F-FDG, thus a comparison of the performance with 68 Ga-PSMA-11 was executed in Chapter 3. This chapter further outlines the requirements for ex vivo usage of 68 Ga-PSMA-11 in humans, based on in vitro results.Part II of this thesis introduces the use of 68 Ga-PSMA-11 PET/CT in primary PCa for CLI optimization. In current clinical practise, patients undergo a diagnostic PSMA PET/CT scan and prostatectomy is scheduled approximately 4 to 6 weeks later. Since patients are included for 68 Ga-PSMA-11 CLI based on their preoperative PSMA PET/CT scan, similar uptake at the time of surgery needs to be ensured. Therefore, repeatability of 68 Ga-PSMA-11 uptake was investigated in a 4-week interval, which is described in Chapter 4. Next, in 68 Ga-PSMA-11 PET/CT scans the optimal time between injection and imaging is based on the contrast of tumour uptake and activity distribution in the rest of the body. It is unknown whether the same time point is required for CLI imaging, as with CLI only the contrast between benign and tumour tissue in the prostate is relevant for ex vivo imaging. Chapter 5 describes dynamic 68 Ga-PSMA-11 PET/CT scans in test-retest setting to evaluate the repeatability of early uptake in the prostate.Part III explores the use of 68 Ga-PSMA-11 CLI, as an intraoperative margin assessment technology. Intraoperative detection of PSM might aid a radical excision, thus improving the patients' outcome. To investigate the feasibility of the technique, the results of the first five patients included in the CLI study are discussed in Chapter 6. This interim analysis showed that CLI is feasible and safe for intraoperative application. Important clinical knowledge was acquired necessary to optimize the acquisition protocol and workflow. The study was continued and the results of CLI accuracy compared to histopathology are reported in Chapter 7. Furthermore, this chapter describes and characterizes a newly identified bioluminescence signal, which might influence the interpretation of the...