PET/MR beeldvorming voor kwantificatie en evaluatie van prostaatspecifiek membraanantigeen en somatostatinereceptor

Positron emission tomography (PET) is a well-established technique combining molecular imaging (PET) with anatomic imaging such as computed tomography (CT) or magnetic resonance imaging (MRI). In order to perform a PET scan, a radiotracer, consisting of a tumor-targeting ligand and a radionuclide such as gallium-68 or fluorine-18, is injected in the systemic circulation of a patient. In nuclear oncology, apart from [¹⁸F]Fluorodeoxyglucose ([¹⁸F]FDG), there are currently two major tumor targets being used for imaging and therapy, i.e. the prostate-specific membrane antigen (PSMA) and somatostatin receptor (SSTR). This thesis covers the use of PET/MR imaging for quantification and evaluation of PSMA and SSTR in primary prostate cancer (PCa) and neuroendocrine tumors (NETs), respectively. Part I of this thesis covers the use of [18F]PSMA-1007 PET/MRI for PSMA imaging in primary PCa. In chapter 1, we evaluated which PSMA immunohistochemistry (IHC) scoring system best quantified PSMA expression, as measured by PSMA PET. We performed a post-hoc analysis on data from 46 patients included in a prospective, monocentric trial investigating high-precision imaging with PSMA PET/MRI in primary unfavourable intermediate and high-risk PCa patients prior to curative surgery with radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND). A comparison of various PSMA IHC scoring systems and the (semi-)quantitative PET parameters Ki, SUVmax and SUVmean was made. We found that the granular, intensity-weighted H-score has the best correlation with PSMA PET quantification and an acceptable interreader agreement. Therefore, we deem H-score the most optimal PSMA IHC scoring system to quantify PSMA expression and predict the PSMA-avidity on [18F]PSMA-1007 PET. Our results demonstrate that an intensity-weighted IHC scoring system best mirrors in-vivo [18F]PSMA-1007 uptake and that it should be used for PSMA quantification on PSMA IHC. The quantification of PSMA IHC could be implemented in routine clinic, complementary to the already available PSMA PET quantification, in certain clinical scenarios such as differentiation between true PSMA negativity or PSMA PET negativity due to other causes. In chapter 2, we investigated the diagnostic performance and interreader agreement of intraprostatic PCa detection, local extension and staging when performing [18F]PSMA-1007 PET in primary PCa, using whole-mount RP specimens as a reference standard. To do so, a post-hoc analysis was performed on data from 66 patients from the same prospective trial as in chapter 1. We observed accurate lesion-level detection of [18F]PSMA-1007 PET for dominant intraprostatic malignant lesions across multiple readers. However, variable diagnostic performance of [18F]PSMA-1007 PET for local tumor extension was seen between readers, highlighting the need for standardized interpretation guidelines and training to improve reproducibility and clinical reliability. In chapter 3, we investigated the relationship between semi-quantitative, qualitative and volumetric [18F]PSMA-1007 PET parameters on the [18F]PSMA-1007 PET scan prior to and following neoadjuvant hormonal treatment and biochemical recurrence-free survival (BCR-FS). Therefore, we performed a post-hoc analysis using the data of a prospective randomized, double-blind, placebo-controlled phase II trial which included 89 high-risk primary PCa patients who received a pelvic [18F]PSMA-1007 PET/MRI prior to and following neoadjuvant hormonal treatment with luteinizing hormone-releasing hormone antagonist plus androgen receptor antagonist or matching placebo. In multivariate Cox regression analysis, we found that the posttreatment PSMA-expressing volume, the pretreatment number of distant metastases and the pretreatment presence of miN1 or miN2 disease were significant independent predictors of BCR-FS. Our results indicate that [18F]PSMA-1007 PET might be used to aid in patient stratification, however further studies are needed to evaluate if patients that have the previously mentioned PSMA PET-based independent predictors of BCR-FS would benefit from additional (neo)adjuvant treatment or need to have a different, personalized treatment plan. Part II of this thesis covers the use of [68Ga]Ga-DOTATATE PET/MRI for SSTR imaging in patients with NETs. In chapter 4, we prospectively investigated which is the best hybrid partner for SSTR PET: CT or MRI with diffusion-weighted sequences. A prospective, monocentric, intra-individual study in which 29 patients received a same-day [68Ga]Ga-DOTATATE PET/CT and PET/MRI was performed. Compared to [68Ga]Ga-DOTATATE PET/CT, [68Ga]Ga-DOTATATE PET/MRI had a higher patient and organ level concordance for malignant tumoral involvement and number of malignant lesions, with a clear added value in bone and liver specifically. Our results imply that SSTR PET/MRI can improve diagnostic confidence in assessment of malignant tumor burden in NET patients, ultimately avoiding additional confirmatory imaging and radiation dose. Therefore, if available, SSTR PET/MRI should be preferred over SSTR PET/CT, particularly in patients with gastroenteropancreatic NETs which frequently metastasize to the liver. However, recent technological and tracer-chemistry breakthroughs have reshaped the nuclear imaging field and may have the potential to dilute the competitive edge of SSTR PET/MRI.