The expression of estrogen receptors (ER), determined in biopsies via immunohistochemistry, is a well-established predictive and prognostic biomarker in breast cancer. Biopsies of metastases are however not always feasible in a patient, as the lesion may be unsafe to biopsy. If one lesion is biopsied, heterogeneity of tumor characteristics amongst lesions throughout the body is still unknown. In vivo imaging of hormone receptors has the potential to guide clinical decision making. The UMCG has extensive experience in PET imaging of ER with the tracer 18F-fluoroestradiol (FES).
In this thesis recommendations on the use and interpretation of FES-PET scans for breast cancer patients are described. For instance we show how previous radiation therapy affects FES PET results. And in a clinical pilot study we show that the FES-PET can identify metastases that are less likely to respond to the combination of letrozole plus palbociclib.
The search for new biomarkers and drug targets continues, and as such the androgen receptor (AR) is of interest. The role of this receptor in breast cancer is reviewed in this thesis. We show that the AR on metastases can be visualized throughout the body by 18F-fluorodihydrotestosterone (FDHT) PET in breast cancer patients and the effect of an AR-blocker can also be visualized.
Prior to further implementation of these novel imaging techniques in routine clinical practice, additional steps are needed. We summarize the route of PET tracers from pre-clinical to first-in-human molecular imaging studies, and the potential steps to implement more PET tracers into clinical practice.

Infective endocarditis is a life-threatening disease that needs an aggressive diagnostic workup and therapeutic management. Current practice is not yet optimised, leaving room for improvement in the care for patients with (suspected) endocarditis. Due to the complexity of this disease, a high level of expertise from the involved medical specialties and a multidisciplinary approach are needed. We have set up a multidisciplinary research team: “IDENTICAL”, acronym for “Improving Diagnosis of Endocarditis and its Therapy with a focus on prosthetIC material”. In this thesis “Endocarditis, improving the chain of care”, we demonstrated that the diagnostic workup for endocarditis could be improved by using non-invasive imaging techniques (FDG-PET/CT, CTA, leukocyte scintigraphy) in addition to echocardiography. Furthermore, identification of pathogens could be achieved more frequently by sonication of heart valves that were surgically explanted during the active phase. There is also room for therapeutic improvement. Dosing antimicrobial agents, such as gentamicin according to a pharmacokinetic model adjusted to the increased volume distribution in patients admitted to the intensive care-unit, led to optimized serum levels in patients with endocarditis. Furthermore, surgical correction with stentless bioprostheses was a valuable option for a more standardized treatment of severe aortic valve endocarditis complicated by extensive abscess formation. Important changes in the daily care of patients were accomplished based on the research described in this thesis: it led to updates of the hospital protocol for endocarditis. Ultimately, regular multidisciplinary Endocarditis Team meetings are needed to reach a final diagnosis and define the most accurate therapy for each patient.

The expression of estrogen receptors (ER), determined in biopsies via immunohistochemistry, is a well-established predictive and prognostic biomarker in breast cancer. Biopsies of metastases are however not always feasible in a patient, as the lesion may be unsafe to biopsy. If one lesion is biopsied, heterogeneity of tumor characteristics amongst lesions throughout the body is still unknown. In vivo imaging of hormone receptors has the potential to guide clinical decision making. The UMCG has extensive experience in PET imaging of ER with the tracer 18F-fluoroestradiol (FES).
In this thesis recommendations on the use and interpretation of FES-PET scans for breast cancer patients are described. For instance we show how previous radiation therapy affects FES PET results. And in a clinical pilot study we show that the FES-PET can identify metastases that are less likely to respond to the combination of letrozole plus palbociclib.
The search for new biomarkers and drug targets continues, and as such the androgen receptor (AR) is of interest. The role of this receptor in breast cancer is reviewed in this thesis. We show that the AR on metastases can be visualized throughout the body by 18F-fluorodihydrotestosterone (FDHT) PET in breast cancer patients and the effect of an AR-blocker can also be visualized.
Prior to further implementation of these novel imaging techniques in routine clinical practice, additional steps are needed. We summarize the route of PET tracers from pre-clinical to first-in-human molecular imaging studies, and the potential steps to implement more PET tracers into clinical practice.

For patients with estrogen receptor (ER) positive breast cancer, endocrine therapy plays a major role in both the adjuvant and palliative setting. For adequate treatment decision-making it is crucial to obtain up-to-date information on the ER-status of the tumor(s), since ER-expression is the sole predictor for response to endocrine therapy. Moreover, ER-status can change during the course of disease in up to 30% of the patients, and therefore treatments based on the ER-status of the primary tumor may be inadequate. Positron emission tomography (PET) imaging of ER-expression by use of the tracer 16α-[18F]fluoro-17β-oestradiol (FES) can give functional information about the ER-status of all lesions within the body. The aim of this thesis is to address the clinical potential of the FES-PET technique in breast and ovarian cancer patients.

This thesis provides farsighted insights in the presence of cardiac sympathetic denervation in different patient groups, the outcome of patients with denervation and the value of SPECT and PET in predicting outcome.
Cardiac amyloidosis is associated with denervation and therefore belonging to one of these indications. Imaging of cardiac sympathetic innervation is of interest in these patients, since amyloid depositions can be present along the sympathetic nerves, and thus leading to electromechanical dissociation. Chapter 2 and 3 investigate the use of [123I]-MIBG for the visualization of denervation in patients with cardiac amyloidosis.
Chapter 4 focuses on the use of [123I]-MIBG for denervation imaging in patients with end-stage chronic kidney failure, who make the transition from the pre-dialysis phase to maintenance hemodialysis (HD). Cardiac sympathetic innervation appears to be already disrupted before the start of maintenance HD.
A third group of interest for cardiac sympathetic innervation imaging is patients with (non-) ischemic heart failure, especially regarding to risk on ventricular arrhythmia and response to resynchronization therapy (CRT). Chapter 5 describes the use of [11C]-mHED in patients with ischemic cardiomyopathy, treated with prophylactic implantable cardioverter defibrillator. Chapter 6 investigates the use of [11C]-mHED in patients with non-ischemic cardiomyopathy treated with CRT.
In Chapter 7 the value of [18F]-FDOPA is evaluated in detecting cardiac metastases and the relationship of these metastases to the presence of typical characteristics of carcinoid heart disease on echocardiography.
Chapter 8 focusses on future perspectives of imaging cardiac sympathetic innervation, with respect to better identification of patients at risk.