title: Radiolabeling strategies for tumor-targeting proteinaceous drugs.
abstract: Owing to their large size proteinaceous drugs offer higher operative information content compared to the small molecules that correspond to the traditional understanding of druglikeness. As a consequence these drugs allow developing patient-specific therapies that provide the means to go beyond the possibilities of current drug therapy. However, the efficacy of these strategies, in particular "personalized medicine", depends on precise information about individual target expression rates. Molecular imaging combines non-invasive imaging methods with tools of molecular and cellular biology and thus bridges current knowledge to the clinical use. Moreover, nuclear medicine techniques provide therapeutic applications with tracers that behave like the diagnostic tracer. The advantages of radioiodination, still the most versatile radiolabeling strategy, and other labeled compounds comprising covalently attached radioisotopes are compared to the use of chelator-protein conjugates that are complexed with metallic radioisotopes. With the techniques using radioactive isotopes as a reporting unit or even the therapeutic principle, care has to be taken to avoid cleavage of the radionuclide from the protein it is linked to. The tracers used in molecular imaging require labeling techniques that provide site specific conjugation and metabolic stability. Appropriate choice of the radionuclide allows tailoring the properties of the labeled protein to the application required. Until the event of positron emission tomography the spectrum of nuclides used to visualize cellular and biochemical processes was largely restricted to iodine isotopes and 99m-technetium. Today, several nuclides such as 18-fluorine, 68-gallium and 86-yttrium have fundamentally extended the possibilities of tracer design and in turn caused the need for the development of chemical methods for their conjugation.
authors.affiliation: Department of Nuclear Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 400, Heidelberg D-69120, Germany.
authors.forename: Grant
authors.initials: G
authors.lastname: Sugiura
authors.affiliation: Department of Nuclear Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 400, Heidelberg D-69120, Germany.
authors.forename: Helen
authors.initials: H
authors.lastname: Kühn
authors.affiliation: Department of Nuclear Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 400, Heidelberg D-69120, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Sauter
authors.affiliation: Department of Nuclear Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 400, Heidelberg D-69120, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Haberkorn
authors.affiliation: Department of Nuclear Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 400, Heidelberg D-69120, Germany. walter.mier@med.uni-heidelberg.de.
authors.forename: Walter
authors.initials: W
authors.lastname: Mier
mesh_terms: D006801:Humans; D007553:Isotope Labeling; D057054:Molecular Imaging; D009369:Neoplasms / Q000188:drug therapy*; D049268:Positron-Emission Tomography; D057285:Precision Medicine; D011506:Proteins / Q000737:chemistry / Q000627:therapeutic use; D011868:Radioisotopes / Q000627:therapeutic use*; D019275:Radiopharmaceuticals
chemical_list: D011506:Proteins; D011868:Radioisotopes; D019275:Radiopharmaceuticals