Current Pharmaceutical Design - Volume 20, Issue 14, 2014

While conventional chemotherapy regimens aim to be cytotoxic against proliferating cells, molecular targeted therapies are directed at specific cancer-associated pathways. To optimize cancer care, an early evaluation of treatment response is warranted for any tumor type - and for any treatment – by using conventional imaging modalities such as ultrasound, CT and MR, FDG-PET or specific radiotracer. FDG-PET is one of Read More

Radiolabelled peptides and proteins have recently gained great interest as theranostics, due to their numerous and considerable advantages over small (organic) molecules. Developmental procedures of these radiolabelled biomolecules start with the radiolabelling process, greatly defined by the amino acid composition of the molecule and the radionuclide used. Depending on the radionuclide selection, radiolabelling starting Read More

This review describes several aspects required for the development of small molecule PET-tracers. Design and selection criteria are important to consider before starting to develop novel PET-tracers. Principles and latest trends in 11C and 18F-radiochemistry are summarized. In addition an update of some new developments in regulatory aspects is supplied.

Receptor tyrosine kinases (RTK) are transmembrane receptors regulating cellular proliferation, differentiation, apoptosis, motility and recruitment of the vasculature. Aberrant expression and/or function of RTK have been detected in many malignant tumors and are considered to be a part of the transformed phenotype. The action of several classes of anti-cancer drugs is based on specific recognition of RTK. Monoclonal antib Read More

Angiogenesis is essential for tumor growth and inhibiting angiogenesis has become an important therapeutic strategy in clinical oncology. Nonetheless, the mechanisms behind anti-angiogenic therapeutics as well as resistance to these drugs remain unclear. With a lack of validated genetic or molecular biomarkers for anti-angiogenic responsiveness, novel methods to identify responsive patients are required. Non-inv Read More

Hypoxia is a characteristic feature of many solid tumors which has been described in a wide range of tumor types. Its presence impairs the effectiveness of common anti-cancer therapies and accordingly, tumor hypoxia has been associated with an aggressive tumor phenotype, poor response to radio- and chemotherapy, and worse prognosis. In order to predict outcome and identify patients with a worse prognosis an Read More

Evasion of apoptosis is one of the hallmarks of cancer and any effective therapy primarily attempts to induce apoptosis. The evaluation of the degree of success of cancer therapy is currently mainly based on clinical and laboratory parameters and in a later stage on tumor shrinkage. However, none of these parameters provide an objective and early analysis of a therapeutic effect. Molecular imaging may provide a to Read More

The G-protein coupled receptor system is involved in a range of cell types and actions and as such has a universal potential in identifying cell functions. The most widely explored system is that of the somatostatin receptors which has been exploited for both imaging and therapy. However, even with this fairly simple system, variation is seen in the behaviour of cells between patients and within different cell population within Read More

Inflammatory and infectious diseases include many different clinical conditions not often well recognised and characterized with conventional radiology and biochemical tests. Radiological techniques (TC, MRI, US) show anatomical changes that usually occur in chronic stages of the disease leading to a delayed diagnosis and therapy. The possibility of Nuclear Medicine imaging to detect biological and biochemical changes in t Read More

MicroRNAs are small noncoding RNAs that have emerged as important regulators of many biological and pathological processes, including those relevant to the development of the heart and cardiovascular disease. Several recent studies using genetic models and profiling of microRNAs have established the important role of these novel molecules in a number of conditions of the heart. These studies have led to a flurry of rese Read More

Inhibition of the renin-angiotensin system (RAS) has been shown to have beneficial effects in cardiovascular disease prognosis and therapy.Discovery of (pro)renin receptor [(P)RR] revealed that (P)RR upon binding to both renin or prorenin in their proenzyme inactive form made them enzymatically active, thus aiding the catalytic conversion of angiotensinogen (AGT) to angiotensin (Ang) I. This binding also transdu Read More

The metabolic syndrome is strongly associated with insulin resistance and visceral obesity and consists of a constellation of factors such as diabetes, hypertension, dyslipidemia and non-alcoholic steatohepatits, which could in concert increase the risk for cardiovascular diseases (CVD). CVD, including myocardial infarction and stroke, is one of the leading causes of morbidity and mortality in the developed countries. Athe Read More

Dipeptidyl peptidases 4 (DPP4) inhibitors are a new class of oral anti-hyperglycemic drugs for the treatment of type 2 diabetes (T2DM). They are also called “incretins” because they act by inhibiting the degradation of endogenous incretin hormones, in particular GLP-1, that mediates their main metabolic effects. DPP4 is an ubiquitous protease that regulates not only glucose and lipid metabolism, but also exhibits several sy Read More

Advanced glycation end products (AGEs) are a heterogenous group of molecules formed during a non-enzymatic reaction between proteins and sugar residues. Recently, AGEs and their receptor (receptor for AGEs; RAGE) play a central role in the pathogenesis of cardiovascular disease (CVD), which accounts for disability and high mortality rate in patients with diabetes. AGEs initiate diabetic micro- and macrovascular co Read More

Nonalcoholic fatty liver disease (NAFLD) is among the most common causes of chronic liver disease in the westernized world and now represents a worldwide public health problem. NAFLD encompasses a broad spectrum of conditions, ranging from simple steatosis (nonalcoholic fatty liver) to nonalcoholic steatohepatitis (NASH). The latter is recognized as a potentially progressive disease that could lead to cirrhosis, liver failure Read More

Chronic kidney disease carries a very high mortality risk, in particular from cardiac diseases. Often heart failure and renal failure coincide, a phenomenon referred to as the cardio renal syndrome. In recent years, it has become clear that not only fibrotic repair but also restoration of damaged kidney and heart can occur and the use of cell therapy has been advanced as a means to activate endogenous repair mechan Read More

Endothelial cell injury is considered to play a critical role for development and progression of atherosclerosis as well as for complications after percutaneous coronary artery interventions in patients with coronary disease. Through the course of human life, the endothelium is constantly replaced and exposure to endothelial cell damaging stimuli, such as cardiovascular risk factors, requires a substantially faster repair and Read More

Atherosclerosis and its thrombotic complications represent the major cause of morbidity and mortality in the industrialized countries. Despite recent advances in the diagnosis and management of cardiovascular disease, a substantial number of patients still die from acute coronary syndromes. Recently, atherosclerotic plaque composition rather than the degree of arterial stenosis has been shown to reflect the plaqu Read More