In this study, we have compared four 68Ga-labeled peptides (three Arg-Gly-Asp (RGD) peptides and substance-P) with two 18F-tracers clinically approved for tumor imaging. We have studied in vitro and in vivo characteristics of selected radiolabeled tracers in a glioblastoma multiforme tumor model. The in vitro part of the study was mainly focused on the evaluation of radiotracers stability under various conditions. We have also determined in vivo stability of studied 68Ga-radiotracers by analysis of murine urine collected at various time points after injection. The in vivo behavior of tested 68Ga-peptides was evaluated through ex vivo biodistribution studies and PET/CT imaging. The obtained data were compared with clinically used 18F-tracers. 68Ga-RGD peptides showed better imaging properties compared to 18F-tracers, i.e., higher tumor/background ratios and no accumulation in non-target organs except for excretory organs.

• Keywords
• 18F-FDG, 18F-FLT, PET, RGD peptides, biodistribution, gallium-68, glioblastoma multiforme,
• MeSH
• Glioblastoma diagnostic imaging   metabolism   MeSH
• Humans MeSH
• Mice, SCID MeSH
• Cell Line, Tumor MeSH
• Brain Neoplasms diagnostic imaging   metabolism   MeSH
• Oligopeptides chemistry   MeSH
• Positron Emission Tomography Computed Tomography MeSH
• Tomography, X-Ray Computed MeSH
• Positron-Emission Tomography methods   MeSH
• Radiopharmaceuticals chemistry   MeSH
• Fluorine Radioisotopes MeSH
• Gallium Radioisotopes chemistry   MeSH
• Tissue Distribution MeSH
• Neoplasm Transplantation MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• arginyl-glycyl-aspartic acid MeSH Browser
• Fluorine-18 MeSH Browser
• Oligopeptides MeSH
• Radiopharmaceuticals MeSH
• Fluorine Radioisotopes MeSH
• Gallium Radioisotopes MeSH

This review covers publications on siderophores applied for molecular imaging applications, mainly for radionuclide-based imaging. Siderophores are low molecular weight chelators produced by bacteria and fungi to scavenge essential iron. Research on these molecules has a continuing history over the past 50 years. Many biomedical applications have been developed, most prominently the use of the siderophore desferrioxamine (DFO) to tackle iron overload related diseases. Recent research described the upregulation of siderophore production and transport systems during infection. Replacing iron in siderophores by radionuclides, the most prominent Ga-68 for PET, opens approaches for targeted imaging of infection; the proof of principle has been reported for fungal infections using 68Ga-triacetylfusarinine C (TAFC). Additionally, fluorescent siderophores and therapeutic conjugates have been described and may be translated to optical imaging and theranostic applications. Siderophores have also been applied as bifunctional chelators, initially DFO as chelator for Ga-67 and more recently for Zr-89 where it has become the standard chelator in Immuno-PET. Improved DFO constructs and bifunctional chelators based on cyclic siderophores have recently been developed for Ga-68 and Zr-89 and show promising properties for radiopharmaceutical development in PET. A huge potential from basic biomedical research on siderophores still awaits to be utilized for clinical and translational imaging.

• Keywords
• Bifunctional chelator, Desferrioxamine, Infection, Siderophores, Triacetylfusarinine C,
• Publication type
• Journal Article MeSH
• Review MeSH

Positron emission tomography (PET) as well as optical imaging (OI) with peptide receptor targeting probes have proven their value for oncological applications but also show restrictions depending on the clinical field of interest. Therefore, the combination of both methods, particularly in a single molecule, could improve versatility in clinical routine. This proof of principle study aims to show that a chelator, Fusarinine C (FSC), can be utilized as scaffold for novel dimeric dual-modality imaging agents. Two targeting vectors (a minigastrin analogue (MG11) targeting cholecystokinin-2 receptor overexpression (CCK2R) or integrin αVβ3 targeting cyclic pentapeptides (RGD)) and a near-infrared fluorophore (Sulfo-Cyanine7) were conjugated to FSC. The probes were efficiently labeled with gallium-68 and in vitro experiments including determination of logD, stability, protein binding, cell binding, internalization, and biodistribution studies as well as in vivo micro-PET/CT and optical imaging in U-87MG αVβ3- and A431-CCK2R expressing tumor xenografted mice were carried out. Novel bioconjugates showed high receptor affinity and highly specific targeting properties at both receptors. Ex vivo biodistribution and micro-PET/CT imaging studies revealed specific tumor uptake accompanied by slow blood clearance and retention in nontargeted tissues (spleen, liver, and kidneys) leading to visualization of tumors at early (30 to 120 min p.i.). Excellent contrast in corresponding optical imaging studies was achieved especially at delayed time points (24 to 72 h p.i.). Our findings show the proof of principle of chelator scaffolding for hybrid imaging agents and demonstrate FSC being a suitable bifunctional chelator for this approach. Improvements to fine-tune pharmacokinetics are needed to translate this into a clinical setting.

• MeSH
• Chelating Agents chemistry   pharmacokinetics   MeSH
• Heterografts MeSH
• Integrin alphaVbeta3 metabolism   MeSH
• Hydroxamic Acids pharmacokinetics   MeSH
• Humans MeSH
• Molecular Probes chemistry   pharmacokinetics   MeSH
• Multimodal Imaging methods   MeSH
• Mice MeSH
• Tumor Cells, Cultured MeSH
• Neoplasms diagnostic imaging   metabolism   MeSH
• Positron Emission Tomography Computed Tomography MeSH
• Gallium Radioisotopes pharmacokinetics   MeSH
• Receptor, Cholecystokinin B metabolism   MeSH
• Ferric Compounds pharmacokinetics   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Chelating Agents MeSH
• fusigen MeSH Browser
• Integrin alphaVbeta3 MeSH
• Hydroxamic Acids MeSH
• Molecular Probes MeSH
• Gallium Radioisotopes MeSH
• Receptor, Cholecystokinin B MeSH
• Ferric Compounds MeSH