A new facile synthetic strategy was developed to prepare bifunctional monophosphinic acid Ln-DOTA derivatives, Gd-DO2AGAP(NBn) and Gd- DO2AGAP(ABn). The relaxivities of the Gd-complexes are enhanced compared to Gd-DOTA. Monophosphinic acid arm of these Gd-complexes affords enhancement of inner sphere water exchange rate due to its steric bulkiness. The different functionalities of DO2AGAP(NBn) were appended in trans positions and are designed to conjugate identical or different vectors according to the potential applications. The conjugation of Gd-DO2AGAP(ABn) with E3 peptide known to target apoptosis was successfully performed and in vivo MRI allowed cell death detection in a mouse model.
- MeSH
- heterocyklické sloučeniny monocyklické chemická syntéza chemie MeSH
- kontrastní látky chemická syntéza chemie MeSH
- magnetická rezonanční tomografie MeSH
- molekulární struktura MeSH
- multimodální zobrazování * MeSH
- myši MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Three magnetic resonance (MR)/fluorescence imaging probes were tested for visualization, cellular distribution, and survival of labeled pancreatic islets in vitro and following transplantation. As T(1) contrast agents (CAs), gadolinium(III) complexes linked to β-cyclodextrin (Gd-F-βCD) or bound to titanium dioxide (TiO2 @RhdGd) were tested. As a T(2) CA, perovskite manganite nanoparticles (LSMO@siF@si) were examined. Fluorescein or rhodamine was incorporated as a fluorescent marker in all probes. Islets labeled with gadolinium(III) CAs were visible as hyperintense spots on MR in vitro, but detection in vivo was inconclusive. Islets labeled with LSMO@siF@si CA were clearly visible as hypointense spots or areas on MR scans in vitro as well as in vivo. All CAs were detected inside the islet cells by fluorescence. Although the vitality and function of the labeled islets was not impaired by any of the tested CAs, results indicate that LSMO@siF@si CA is a superior marker for islet labeling, as it provides better contrast enhancement within a shorter scan time.
- MeSH
- beta-cyklodextriny chemie MeSH
- fluorescenční barviva chemie MeSH
- fluorescenční mikroskopie MeSH
- gadolinium chemie MeSH
- kontrastní látky chemie diagnostické užití MeSH
- kovové nanočástice chemie diagnostické užití MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- Langerhansovy ostrůvky cytologie metabolismus radiografie MeSH
- magnetická rezonanční tomografie MeSH
- potkani inbrední LEW MeSH
- sloučeniny manganu chemie MeSH
- titan chemie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Multimodal imaging-therapeutic nanoprobe TiO(2)@RhdGd was prepared and successfully used for in vitro and in vivo cell tracking as well as for killing of cancer cells in vitro. TiO(2) nanoparticles were used as a core for phosphonic acid modified functionalities, responsible for contrast in MRI and optical imaging. The probe shows high (1)H relaxivity and relaxivity density values. Presence of fluorescent dye allows for visualization by means of fluorescence microscopy. The applicability of the probe was studied, using mesenchymal stem cells, cancer HeLa cells, and T-lymphocytes. The probe did not exhibit toxicity in any of these systems. Labeled cells were successfully visualized in vitro by means of fluorescence microscopy and MRI. Furthermore, it was shown that the probe TiO(2)@RhdGd can be changed into a cancer cell killer upon UV light irradiation. The above stated results represent a valuable proof of a principle showing applicability of the probe design for diagnosis and therapy.
- MeSH
- afinitní značky chemická syntéza chemie farmakologie MeSH
- fluorescenční barviva chemická syntéza chemie farmakologie MeSH
- fluorescenční mikroskopie MeSH
- gadolinium MeSH
- HeLa buňky MeSH
- komplexní sloučeniny chemická syntéza chemie farmakologie MeSH
- kyseliny fosforité chemická syntéza chemie farmakologie MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mezenchymální kmenové buňky metabolismus MeSH
- myši MeSH
- nanočástice MeSH
- protinádorové látky chemická syntéza chemie farmakologie MeSH
- screeningové testy protinádorových léčiv MeSH
- T-lymfocyty metabolismus MeSH
- titan chemie farmakologie MeSH
- ultrafialové záření MeSH
- viabilita buněk účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In magnetic resonance imaging (MRI), paramagnetic complexes are utilized as contrast agents. Much attention has been paid to the development of new contrast agents responsive to pH, temperature or concentration of various components of body liquids. We report a new type of MRI probe sensing the concentrations of calcium and magnesium in biological media. The ligand do3ap(BP) combines a dota-like chelator with a bisphosphonate group. In the complex, the Gd(III) ion is entrapped in the macrocyclic cavity whereas the bisphosphonate group is not coordinated and therefore is available for coordination with endogenous metal ions. In the presence of metal ions, Gd-do3ap(BP) appears to show formation of coordination oligomers leading to an unprecedented increase in r(1) up to 200-500%. The extremely high relaxivity response makes this type of compound interesting for further studies as MRI ion-responsive probes for biomedical research.
In clinical practice the imaging of bone tissue is based almost exclusively on x-ray or radiochemical methods. Alternative methods, such as MRI and optical imaging, can provide not only anatomical, but also physiological information, due to their ability to reflect the properties of body fluids (temperature, pH and concentration of ions). In this article we review bone targeting probes for MRI and fluorescence imaging. As bone targeting is mainly associated with phosphonate and bisphosphonate derivatives, we also focus on their sorption behavior. Also discussed in detail is the limitation of using bone-targeting probes for MRI and optical imaging mainly due to their long-time retention in bone tissue and the low permeability of tissues for light.
- MeSH
- fluorescenční barviva chemie metabolismus MeSH
- kosti a kostní tkáň cytologie metabolismus MeSH
- kovy chemie MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- molekulární struktura MeSH
- molekulární zobrazování metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
A new phosphinic-acid DOTA-like ligand, DO3AP(BP), containing a geminal bis(phosphonic acid) moiety as a highly effective bone-seeking group, was synthesized in high yield. Its crystal structure was determined by X-ray analysis. Complexation with lanthanide(iii) ions occurs under mild conditions (pH = 8-9, 25 degrees C, 2-3 h). (1)H, (31)P, and (17)O NMR spectroscopy show that DO3AP(BP) forms nine-coordinated lanthanide(iii) complexes with one water molecule in the first coordination sphere except for Ln = Er-Lu, which have in addition a species without lanthanide(iii)-bound water. Selective formation of only two diastereomers (out of four possible) suggests that the coordinated phosphinate phosphorus atom occurs exclusively in one of the enantiomeric forms. The ratio of the twisted square antiprism (TSA) and square antiprism (SA) diastereomers changes along the lanthanide series; the gadolinium(iii) complex has about 35% of the TSA species. The bis(phosphonate) moiety remains free for anchoring to osseous tissue. The (1)H longitudinal relaxivity of the Gd-DO3AP(BP) complex (r(1) = 7.4 s(-1) mM(-1), 20 MHz, 25 degrees C, pH = 7.5) is unexpectedly high compared to that of other monohydrated chelates of similar size thanks to a significant contribution from the second hydration sphere. The water residence time tau(M)(298) is 198 ns. Further increase in the relaxivity was observed in the presence of Zn(ii), Mg(ii) or Ca(ii) ions, due to formation of coordination polymers. Slowing down of the tumbling rate of the Gd-DO3AP(BP) complex upon adsorption on hydroxyapatite also leads to an increase of the relaxivity (r(1) = 17 s(-1) mM(-1), 20 MHz, 25 degrees C, pH = 7.5).
- MeSH
- chelátory chemie MeSH
- diagnostické zobrazování metody MeSH
- financování organizované MeSH
- gadolinium chemie MeSH
- heterocyklické sloučeniny monocyklické chemie MeSH
- hydroxyapatit MeSH
- kalcinóza patologie radiografie radioterapie MeSH
- kontrastní látky chemie MeSH
- kosti a kostní tkáň cytologie metabolismus MeSH
- krystalografie rentgenová MeSH
- lanthanoidy chemie MeSH
- molekulární struktura MeSH
- organofosfonáty chemie MeSH
