Radionuclide imaging of tumor angiogenesis.
Angiogenesis is a multistep process regulated by pro- and antiangiogenic factors. In order to grow and metastasize, tumors need a constant supply of oxygen and nutrients. For growth beyond 1-2 mm in size, tumors are dependent on angiogenesis. Inhibition of angiogenesis is a new cancer treatment strategy that is now widely investigated clinically. Researchers have begun to search for objective measures that indicate pharmacologic responses to antiangiogenic drugs. Therefore, there is a great interest in techniques to visualize angiogenesis in growing tumors noninvasively. Several markers have been described that are preferentially expressed on newly formed blood vessels in tumors (alpha(v)beta(3) integrin, vascular endothelial growth factor, and its receptor, prostate-specific membrane antigen) and in the extracellular matrix surrounding newly formed blood vessels (extra domain B of fibronectin, Tenascin-C, matrix metalloproteinases, and Robo-4). Several ligands targeting these markers have been tested as a radiotracer for imaging angiogenesis in tumors. The potential of some of these tracers, such as radiolabeled cyclic RGD peptides and radiolabeled anti-PSMA antibodies, has already been tested in cancer patients, while for markers such as Robo-4, the ligand has not yet been identified. In this review, an overview on the currently used nuclear imaging probes for noninvasive visualization of tumor angiogenesis is given.
Dijkgraaf
Ingrid
I
Department of Nuclear Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. I.Dijkgraaf@nucmed.umcn.nl
Boerman
Otto C
OC
D017398:Alternative Splicing; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D004730:Endothelium, Vascular / Q000201:enzymology / Q000473:pathology; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007205:Indium Radioisotopes; D039302:Integrin alphaVbeta3 / Q000502:physiology; D008279:Magnetic Resonance Imaging; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000188:drug therapy; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging* / Q000188:drug therapy; D009842:Oligopeptides / Q000032:analysis; D049268:Positron-Emission Tomography; D011971:Receptors, Immunologic / Q000032:analysis; D018000:Receptors, Peptide / Q000032:analysis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000032:analysis / Q000235:genetics
D020533:Angiogenesis Inhibitors; D007205:Indium Radioisotopes; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; C051382:arginyl-glycyl-aspartic acid directed cell adhesion receptor; D019788:Fluorodeoxyglucose F18; C047981:arginyl-glycyl-aspartic acid; D040262:Receptors, Vascular Endothelial Growth Factor; D020782:Matrix Metalloproteinases