title: Comparative Assessment of Complex Stabilities of Radiocopper Chelating Agents by a Combination of Complex Challenge and in vivo Experiments.
abstract: For (64) Cu radiolabeling of biomolecules to be used as in vivo positron emission tomography (PET) imaging agents, various chelators are commonly applied. It has not yet been determined which of the most potent chelators--NODA-GA ((1,4,7-triazacyclononane-4,7-diyl)diacetic acid-1-glutaric acid), CB-TE2A (2,2'-(1,4,8,11-tetraazabicyclo[6.6.2]hexadecane-4,11-diyl)diacetic acid), or CB-TE1A-GA (1,4,8,11-tetraazabicyclo[6.6.2]hexadecane-4,11-diyl-8-acetic acid-1-glutaric acid)--forms the most stable complexes resulting in PET images of highest quality. We determined the (64) Cu complex stabilities for these three chelators by a combination of complex challenge and an in vivo approach. For this purpose, bioconjugates of the chelating agents with the gastrin-releasing peptide receptor (GRPR)-affine peptide PESIN and an integrin αv β3 -affine c(RGDfC) tetramer were synthesized and radiolabeled with (64) Cu in excellent yields and specific activities. The (64) Cu-labeled biomolecules were evaluated for their complex stabilities in vitro by conducting a challenge experiment with the respective other chelators as challengers. The in vivo stabilities of the complexes were also determined, showing the highest stability for the (64) Cu-CB-TE1A-GA complex in both experimental setups. Therefore, CB-TE1A-GA is the most appropriate chelating agent for *Cu-labeled radiotracers and in vivo imaging applications.
authors.affiliation: Biomedical Chemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany).|Molecular Imaging and Radiochemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany).
authors.forename: Shanna
authors.initials: S
authors.lastname: Litau
authors.affiliation: Biomedical Chemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany).|Molecular Imaging and Radiochemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany).
authors.forename: Uwe
authors.initials: U
authors.lastname: Seibold
authors.affiliation: Biomedical Chemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany).
authors.forename: Alicia
authors.initials: A
authors.lastname: Vall-Sagarra
authors.affiliation: Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Im Neuenheimer Feld 329, 69120 Heidelberg (Germany).
authors.forename: Gert
authors.initials: G
authors.lastname: Fricker
authors.affiliation: Molecular Imaging and Radiochemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany).
authors.forename: Björn
authors.initials: B
authors.lastname: Wängler
authors.affiliation: Biomedical Chemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany). Carmen.Waengler@medma.uni-heidelberg.de.
authors.forename: Carmen
authors.initials: C
authors.lastname: Wängler
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D003301:Copper Radioisotopes; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015394:Molecular Structure; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D002614:Chelating Agents; D003301:Copper Radioisotopes; D019275:Radiopharmaceuticals
keywords: complex stability; copper-64; in vivo imaging; positron emission tomography; radiochemistry