The Role of VEGF Receptors as Molecular Target in Nuclear Medicine for Cancer Diagnosis and Combination Therapy

SIMPLE SUMMARY: The rapid development of diagnostic and therapeutic methods of the cancer treatment causes that these diseases are becoming better known and the fight against them is more and more effective. Substantial contribution in this development has nuclear medicine that enables very early cancer diagnosis and early start of the so-called targeted therapy. This therapeutic concept compared to the currently used chemotherapy, causes much fewer undesirable side effects, due to targeting a specific lesion in the body. This review article discusses the possible applications of radionuclide-labelled tracers (peptides, antibodies or synthetic organic molecules) that can visualise cancer cells through pathological blood vessel system in close tumour microenvironment. Hence, at a very early step of oncological disease, targeted therapy can involve in tumour formation and growth. ABSTRACT: One approach to anticancer treatment is targeted anti-angiogenic therapy (AAT) based on prevention of blood vessel formation around the developing cancer cells. It is known that vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptors (VEGFRs) play a pivotal role in angiogenesis process; hence, application of angiogenesis inhibitors can be an effective approach in anticancer combination therapeutic strategies. Currently, several types of molecules have been utilised in targeted VEGF/VEGFR anticancer therapy, including human VEGF ligands themselves and their derivatives, anti-VEGF or anti-VEGFR monoclonal antibodies, VEGF binding peptides and small molecular inhibitors of VEGFR tyrosine kinases. These molecules labelled with diagnostic or therapeutic radionuclides can become, respectively, diagnostic or therapeutic receptor radiopharmaceuticals. In targeted anti-angiogenic therapy, diagnostic radioagents play a unique role, allowing the determination of the emerging tumour, to monitor the course of treatment, to predict the treatment outcomes and, first of all, to refer patients for AAT. This review provides an overview of design, synthesis and study of radiolabelled VEGF/VEGFR targeting and imaging agents to date. Additionally, we will briefly discuss their physicochemical properties and possible application in combination targeted radionuclide tumour therapy.