Prostate carcinoma (PCa) is one of the most frequently diagnosed cancers in men worldwide and the second most common cause of cancer death in 2021. The etiology of PCa is still largely unknown, but some factors promote tumor development and progression in the prostate. These factors include environmental factors, genetic predisposition, and especially age. At >65 years, the risk of PCa increases exponentially and the mortality rate can be linked to age. Patients can remain symptom-free in the early PCa stage. As the tumor progresses, symptoms may include bone pain, urinary dysfunction, weight loss, and anemia. In the course, metastases develop in the body, initially in local lymph nodes or bones. PCa is usually diagnosed at an intermediate or terminal stage, which makes it challenging for treatment and recovery. Human prostate tissue consists of three main types of epithelial cells: luminal, basal, and neuroendocrine. These epithelial cell types are also found in the prostate of male mice, making a mouse model ideal for PCa research. PCa develops mainly from luminal cells, but basal cells can also act as prostate cancer-initiating cells. Several processes are involved in the pathophysiology of PCa progression: precursor intraepithelial neoplasia, followed by localized PCa and advanced PCa. Progression of prostate cancer occurs in several phases and is associated with various genetic, molecular, and cellular changes, e.g. changes in androgens. The prostate-specific antigen (PSA) is involved in the regulation of androgens. PSA is mainly used in oncology as a biomarker for PCa but is criticized for its low specificity. The tumor microenvironment also plays an important role in tumorigenesis, being involved in numerous processes such as tumor development, metastasis, and the development of resistance to therapy. Stromal cells include fibroblasts, macrophages, lymphocytes, mast cells, endothelial cells, pericytes, smooth muscle cells, and extracellular matrix (ECM) proteins. The current clinical reference standard to diagnose PCa is the histologic evaluation by transrectal ultrasound-guided systematic core needle biopsy. In addition, rectal palpation, biomarker determination in the blood, and different imaging techniques are used in the diagnostic workup. These imaging techniques include transrectal ultrasound (TRUS), computed tomography (CT), positron emission tomography (PET), and conventional magnetic resonance imaging (MRI). For MRI examinations, a gadolinium-based imaging probe is often used to obtain strong contrast images of the tissue structure. Molecular MRI is an intensively researched field since it allows in vivo visualization of biological and biochemical processes at the molecular and cellular levels. This work aimed to apply specific molecular probes in PCa using a probe that specifically binds to elastic fibers and visualizes pathological changes quantitatively. Secondly, iron-oxide particles, ferumoxytol, were used, whereby the particles are phagocytosed by macrophages in the tumor and therefore enable the evaluation of cellular characteristics. The experiments were performed in a small animal xenograft prostate tumor model, firstly by investigating the feasibility of each molecular probe and secondly by comparing different tumor volumes. Both imaging probes, the elastin-specific probe, and ferumoxytol, showed a good visualization and enabled an improved differentiation of PCa on MRI compared to an unenhanced scan. The tumor sizes were significantly different from each other, which could be visualized and quantified in the imaging as well as in the pathological and biological examinations. The studies demonstrate that molecular MR imaging has great potential to improve the diagnosis, cellular characterization, risk assessment, and treatment monitoring of prostate cancer. Additionally, avoiding invasive surgery for obtaining punch biopsies would reduce the risks of complications in patients. Molecular probes improve understanding of tumor development and biology.
