title: Improving the stability of peptidic radiotracers by the introduction of artificial scaffolds: which structure element is most useful?
abstract: Peptidic radiotracers are highly potent substances for the specific in vivo imaging of various biological targets with Single Photon Emission Computed Tomography and Positron Emission Tomography. However, some radiolabeled peptides such as bombesin analogs were shown to exhibit only a limited stability, hampering a successful target visualization. One option to positively influence the stability of radiolabeled peptides is the introduction of certain artificial molecular scaffolds. In order to comparatively assess the influence of different structure elements on the stability of radiolabeled peptides and to identify those structure elements being most useful for peptide radiotracer stabilization, several monomeric and dimeric bombesin derivatives were synthesized, exhibiting differing molecular designs and the chelator NODAGA for (68) Ga-labeling. The radiolabeled peptides were evaluated regarding their in vitro stability in human serum to determine the influence of the introduced molecular scaffolds on the peptides' serum stabilities. The results of the evaluations showed that the introduction of scaffold structures and the overall molecular design have a substantial impact on the stabilities of the resulting peptidic radiotracers. But besides some general trends found using certain scaffold structures, the obtained results point to the necessity to empirically assess their influence on stability for each susceptible peptidic radiotracer individually.
authors.affiliation: University of Applied Sciences, Campus Zweibrücken, Zweibrücken, Germany.|Biomedical Chemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Mannheim, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Bacher
authors.affiliation: Biomedical Chemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Mannheim, Germany.|Molecular Imaging and Radiochemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Mannheim, Germany.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Fischer
authors.affiliation: Biomedical Chemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Mannheim, Germany.|Molecular Imaging and Radiochemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Mannheim, Germany.
authors.forename: Shanna
authors.initials: S
authors.lastname: Litau
authors.affiliation: Department of Oncology, Division Oncological Imaging, University of Alberta, Edmonton, Canada.
authors.forename: Ralf
authors.initials: R
authors.lastname: Schirrmacher
authors.affiliation: Molecular Imaging and Radiochemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Mannheim, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Wängler
authors.affiliation: University of Applied Sciences, Campus Zweibrücken, Zweibrücken, Germany.
authors.forename: Marko
authors.initials: M
authors.lastname: Baller
authors.affiliation: Biomedical Chemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Mannheim, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Wängler
mesh_terms: D000085:Acetates / Q000737:chemistry*; D001839:Bombesin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D005710:Gallium Radioisotopes / Q000737:chemistry*; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D006801:Humans; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry; D055550:Protein Stability; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D044967:Serum; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: C572723:1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane; D000085:Acetates; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D010446:Peptide Fragments; D019275:Radiopharmaceuticals; C118536:bombesin (7-14); D001839:Bombesin
keywords: 68Ga; molecular design; peptide; radiotracer; serum stability