Radiopeptides for Targeted Tumour Therapy and the Kidney Melis, M.L. 2010-12-16 Doctoral Thesis

One of the main causes of morbidity and mortality in the modern world is cancer. According to World Health Organization (WHO) reports the worldwide mortality rate due to malignant neoplasms is 12.5%, but in the Western world this is about 30% in the 45-75 year age group. In The Netherlands the prevalence of different types of cancer varies between sexes; amongst men prostate cancer (21%) and amongst women breast cancer (33%) are the most frequently diagnosed types, expressed as percentage of all registered tumour patients. Lung (16% men, 8% women) and colorectal carcinomas (13%) are major cancers as well (The Netherlands Cancer Registry). In this respect the incidence of cancers from neuroendocrine origin, the main tumour type discussed in this thesis, is very low; less than 0.1%. Because of slow progression of the disease the prevalence is much higher, however. Many different clinical tools are available to detect tumours. Several imaging modalities can be employed to visualize tumours and their metastases, including radiography using X-rays, ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and nuclear imaging. The latter includes gamma (γ)-radiation, both planar- and single-photon emission computed tomography- (SPECT) imaging and positron (β+) emission tomography (PET). For therapy surgery is the first option, followed by (adjuvant) chemotherapy, external beam radiation therapy (EBRT), radionuclide therapy, or combinations thereof. The ideal situation during therapy would be that only, or at least primarily, tumour cells are removed, damaged or killed, while harmful side effects on normal cells and tissues are reduced to a minimum. Any undesirable effects may be unavoidable though. Over the last decades progress has been achieved concerning specific targeting of tumour cells. This concept is based on the presence of biomarkers expressed only, mainly or in high density on malignant cells in comparison to healthy cells. Targeting agents with specific ligand- binding properties to these biomarkers, can be applied as tumour targeting tools for diagnostic or therapeutic use. Diagnostic imaging is feasible when γ- or β+-emitting radionuclides or other imaging tags are labelled to tumour-specific antibodies or peptides. These antibodies and peptides can have a therapeutic effect as such, but when conjugated with a therapeutic alpha (α)- or beta (β—)-emitting radionuclide or other cytotoxic compound DNA damage can be induced to destroy tumour cells expressing the biomarkers, while sparing healthy tissues.

http://repub.eur.nl/res/pub/21854/101216_Melis%2C%20Maatje%20Lena.pdf