This thesis explores new applications of nuclear imaging and therapy in patients with hepatocellular carcinoma (HCC) and neuroendocrine tumors (NET). These diseases are often detected late, making curative therapy not always possible. Developments in positron emission tomography (PET) and radionuclide therapy have led to new nuclear agents. The aim of this thesis is to provide insight into several new applications of current and new tracers in the diagnosis and treatment of HCC and NET.

One of the investigated tracers is 18F-DOPA, which is currently used for NET tumors that are negative on 68Ga-labeled somatostatin analog (SSA) PET scans. Our study confirms the equivalent detection of 18F-DOPA in tumor detection compared to 68Ga-SSAs. Selective internal radiation therapy (SIRT) uses yttrium-90 radioactive resin spheres that are intravascularly injected into the liver. Higher than usual dosages (>120 Gy) appear to lead to better results in tumor reduction and the effects not only seem to be greater but also longer lasting.

Furthermore, we demonstrated that 11C-Choline and 18F-FDG together find more tumors that are relevant for clinical decision-making in patients suspected of HCC recurrence. The thesis also offers two prospective study protocols, namely a comparison of 68Ga-DOTA-TOC with the new somatostatin tracer 18F-SiTATE in NET and a comparison of ablation with SIRT as a bridge strategy in liver transplantation.

These results suggest that broader use of 18F-DOPA in PET diagnosis of NET is possible and that higher tumor-targeted dosages in SIRT can lead to better treatment.

The most specific and sensitive imaging modality for visualizing and measuring human (patho)physiology in vivo is Positron Emission Tomography (PET). PET is a firmly established biomedical imaging modality with applications in routine clinical diagnostic imaging, but also in research, including clinical trials. Over the past years, PET technology development brought new innovative PET systems to the commercial market: silicon photomultiplier (SiPM)-based or ‘digital’ PET systems, and large axial field-of-view or ‘total body’ PET systems. This thesis describes the technical performance characteristics of these new PET technologies and, in addition, associated optimization of image quality and activity administration is reported. Furthermore, clinical implications and future perspectives regarding these innovations in the field of nuclear medicine and molecular imaging and other medical disciplines are discussed.

The aim of this thesis was to investigate the role of imaging in the management of PTLD, with focus on [18F]FDG PET/CT. Additionally, we set out to explore new diagnostic methods with potential for clinical translation. In Part I (chapters 2-7), we reviewed the published literature on the role of different imaging modalities in PTLD and evaluated the diagnostic performance of [18F]FDG PET/CT for PTLD lesion detection in adults and children. Furthermore, we explored the role of [18F]FDG PET/CT semiquantification in PTLD for lesion classification and prognostication. In Part II (chapters 8-10) we proceeded to explore new avenues of research including: radiomics, identification of radiotracers adjunct to [18F]FDG and cfDNA analysis.