Radiolabeled small molecule inhibitors of VEGFR - recent advances

Curr Pharm Des. 2012;18(20):2867-74. doi: 10.2174/138161212800672796.

Abstract

The vascular endothelial growth factor (VEGF) is a key regulator of neovascularization and an elevated level of VEGF is known to correlate with increased metastatic invasion. Anti-angiogenic therapies focus on targeted inhibition of overexpressed growth factors with the aim of suppressing tumor proliferation, one approach is the attempt to block the intracellular tyrosine kinase at the adenosine triphosphate (ATP) binding site with small molecule inhibitors. For most effective treatment these targeted tumor therapies are accompanied with a more sensitive need for dose optimization and monitoring the therapeutic response. Direct non-invasive molecular imaging of tumor vascularization and of the angiogenic process in vivo would facilitate the selection of patients and help to evaluate the efficacy of an anti-angiogenic therapy. Radionuclide-based imaging technologies like PET and SPECT are progressively affecting the clinical diagnosis and treatment of cancer. A non-invasive and a reliable quantitative method to determine in vivo the levels of VEGFR expression using radiolabeled small molecules would help to develop a customized VEGFR-targeted chemotherapy. This review will give an overview on radiolabeled derivatives of small molecule VEGFR inhibitors basing on lead structures that have been approved or have reached clinical trials. It is covering aspects of the radiosynthesis as well the results of radiopharmacological and biological evaluation.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems
  • Drug Design
  • Drug Monitoring / methods
  • Humans
  • Molecular Imaging / methods
  • Neoplasms / blood supply
  • Neoplasms / diagnostic imaging
  • Neoplasms / drug therapy
  • Neovascularization, Pathologic / diagnostic imaging
  • Neovascularization, Pathologic / drug therapy*
  • Patient Selection
  • Radionuclide Imaging
  • Radiopharmaceuticals / administration & dosage
  • Radiopharmaceuticals / chemistry
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Radiopharmaceuticals
  • Vascular Endothelial Growth Factor A