PURPOSE: Combining specific and quantitative F-19 magnetic resonance imaging (MRI) with sensitive and convenient optical imaging provides complementary information about the distribution and viability of transplanted pancreatic islet grafts. In this study, pancreatic islets (PIs) were labeled with positively charged multimodal nanoparticles based on poly(lactic-co-glycolic acid) (PLGA-NPs) with encapsulated perfluoro-15-crown-5-ether and the near-infrared fluorescent dye indocyanine green. PROCEDURES: One thousand and three thousand bioluminescent PIs were transplanted into subcutaneous artificial scaffolds, which served as an alternative transplant site. The grafts were monitored using in vivo F-19 MR, fluorescence, and bioluminescence imaging in healthy rats for 2 weeks. RESULTS: Transplanted PIs were unambiguously localized in the scaffolds by F-19 MRI throughout the whole experiment. Fluorescence was detected in the first 4 days after transplantation only. Importantly, in vivo bioluminescence correlated with the F-19 MRI signal. CONCLUSIONS: We developed a trimodal imaging platform for in vivo examination of transplanted PIs. Fluorescence imaging revealed instability of the fluorescent dye and its limited applicability for longitudinal in vivo studies. A correlation between the bioluminescence signal and the F-19 MRI signal indicated the fast clearance of PLGA-NPs from the transplantation site after cell death, which addresses a major issue with intracellular imaging labels. Therefore, the proposed PLGA-NP platform is reliable for reflecting the status of transplanted PIs in vivo.

• Klíčová slova
• F-19 magnetic resonance imaging, Nanoparticles, Optical imaging, Pancreatic islets, Transplantation,
• MeSH
• endocytóza MeSH
• fluor chemie   MeSH
• fluorescence MeSH
• Langerhansovy ostrůvky diagnostické zobrazování   MeSH
• luminiscenční měření * MeSH
• magnetická rezonanční tomografie * MeSH
• modely u zvířat MeSH
• molekulární zobrazování * MeSH
• potkani inbrední LEW MeSH
• potkani transgenní MeSH
• přežití tkáně MeSH
• tkáňové podpůrné struktury chemie   MeSH
• transplantace Langerhansových ostrůvků * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fluor MeSH

Over the last few years, the development and relevance of 19F magnetic resonance imaging (MRI) for use in clinical practice has emerged. MRI using fluorinated probes enables the achievement of a specific signal with high contrast in MRI images. However, to ensure sufficient sensitivity of 19F MRI, fluorine probes with a high content of chemically equivalent fluorine atoms are required. The majority of 19F MRI agents are perfluorocarbon emulsions, which have a broad range of applications in molecular imaging, although the content of fluorine atoms in these molecules is limited. In this review, we focus mainly on polymer probes that allow higher fluorine content and represent versatile platforms with properties tailorable to a plethora of biomedical in vivo applications. We discuss the chemical development, up to the first imaging applications, of these promising fluorine probes, including injectable polymers that form depots that are intended for possible use in cancer therapy.

• Klíčová slova
• 19F MRI probe, Fluorine, Magnetic resonance imaging (MRI), Molecular imaging, Polymer,
• MeSH
• fluor chemie   MeSH
• fluorokarbony chemie   MeSH
• koncentrace vodíkových iontů MeSH
• kontrastní látky chemie   MeSH
• lidé MeSH
• molekulární sondy chemie   MeSH
• molekulární zobrazování přístrojové vybavení   metody   MeSH
• myši MeSH
• polymery chemie   MeSH
• radiační rozptyl MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• světlo MeSH
• teplota MeSH
• zobrazování fluorovou magnetickou rezonancí metody   trendy   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• fluor MeSH
• fluorokarbony MeSH
• kontrastní látky MeSH
• molekulární sondy MeSH
• polymery MeSH
• reaktivní formy kyslíku MeSH

OBJECTIVE: 19F MRI requires biocompatible and non-toxic soluble contrast agents with high fluorine content and with suitable 19F relaxation times. Probes based on a DOTP chelate with 12 magnetically equivalent fluorine atoms (DOTP-tfe) and a lanthanide(III) ion shortening the relaxation times were prepared and tested. METHODS: Complexes of DOTP-tfe with trivalent paramagnetic Ce, Dy, Ho, Tm, and Yb ions were synthetized and characterized. 19F relaxation times were determined and compared to those of the La complex and of the empty ligand. In vitro and in vivo 19F MRI was performed at 4.7 T. RESULTS: 19F relaxation times strongly depended on the chelated lanthanide(III) ion. T1 ranged from 6.5 to 287 ms, T2 from 3.9 to 124.4 ms, and T2* from 1.1 to 3.1 ms. All complexes in combination with optimized sequences provided sufficient signal in vitro under conditions mimicking experiments in vivo (concentrations 1.25 mM, 15-min scanning time). As a proof of concept, two contrast agents were injected into the rat muscle; 19F MRI in vivo confirmed the in vivo applicability of the probe. CONCLUSION: DOTP-based 19F probes showed suitable properties for in vitro and in vivo visualization and biological applications. The lanthanide(III) ions enabled us to shorten the relaxation times and to trim the probes according to the actual needs. Similar to the clinically approved Gd3+ chelates, this customized probe design ensures consistent biochemical properties and similar safety profiles.

• Klíčová slova
• Fluorine-19 magnetic resonance imaging, Lanthanide series elements, Macrocyclic ligand complexes, Molecular probes, Phosphinic acid complexes, Relaxation times,
• MeSH
• chelátory chemie   MeSH
• fluor chemie   MeSH
• ionty MeSH
• kontrastní látky chemie   MeSH
• krysa rodu Rattus MeSH
• lanthanoidy chemie   MeSH
• ligandy MeSH
• magnetismus MeSH
• molekulová hmotnost MeSH
• oxazoly chemie   MeSH
• pyrimidinony chemie   MeSH
• zobrazování fluorovou magnetickou rezonancí * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 2,3-dihydro-5H-oxazolo(3,2-a)thieno(3,2-d)pyrimidin-5-one MeSH Prohlížeč
• chelátory MeSH
• fluor MeSH
• ionty MeSH
• kontrastní látky MeSH
• lanthanoidy MeSH
• ligandy MeSH
• oxazoly MeSH
• pyrimidinony MeSH