Magnetic resonance (MR) imaging is advantageous because it concurrently provides anatomic, functional, and molecular information. MR molecular imaging can combine the high spatial resolution of this established clinical modality with molecular profiling in vivo. However, as a result of the intrinsically low sensitivity of MR imaging, high local concentrations of biological targets are required to generate discernable MR contrast. We hypothesize that the prostate‐specific membrane antigen (PSMA), an attractive target for imaging and therapy of prostate cancer, could serve as a suitable biomarker for MR‐based molecular imaging. We have synthesized three new high‐affinity, low‐molecular‐weight GdIII‐based PSMA‐targeted contrast agents containing one to three GdIII chelates per molecule. We evaluated the relaxometric properties of these agents in solution, in prostate cancer cells, and in an in vivo experimental model to demonstrate the feasibility of PSMA‐based MR molecular imaging. 相似文献
Responsive or smart magnetic resonance imaging (MRI) contrast agents are molecular sensors that alter the MRI signal upon changes in a particular parameter in their microenvironment. Consequently, they could be exploited for visualization of various biochemical events that take place at molecular and cellular levels. In this study, a set of dual‐frequency calcium‐responsive MRI agents are reported. These are paramagnetic, fluorine‐containing complexes that produce remarkably high MRI signal changes at the 1H and 19F frequencies at varying Ca2+ concentrations. The nature of the processes triggered by Ca2+ was revealed, allowing a better understanding of these complex systems and their further improvement. The findings indicate that these double‐frequency tracers hold great promise for development of novel functional MRI methods. 相似文献
Iron oxide nanoparticles as contrast agents are reported to effectively improve magnetic resonance imaging of tissues and cells. In this work, cleaved iron oxide nanoparticles (CIONPs) were generated from hydrophobic FeO nanoparticles (HIONPs) by coating their surfaces with PEG‐phospholipids, oxidizing them under water, and slowly removing the residual FeO phase in phthalate buffer. The synthesized CIONPs showed good r2 values of up to 258 s?1 mM ?1. Thus, the CIONPs can be employed as vectors for drug delivery due to their unique structure with an empty inner space, which enables their use in a wide range of applications. 相似文献
A novel bimodal fluorescence/MRI probe based on a cyclodextrin scaffold has been synthesized and characterized. The final agent employs the fluorescein (F) functionality as a fluorescence marker and the GdIII complex of a macrocyclic DOTA‐based ligand (GdL) having one aminobenzyl‐phosphinic acid pendant arm as an MRI probe, and has a statistical composition of (GdL)6.9‐F0.1‐β‐CD. Slow rotational dynamics (governed by a very rigid cyclodextrin scaffold) combined with fast water exchange (ensured by the chosen macrocyclic ligand) resulted in a high relaxivity of ~22 s?1 mM ?1 per GdIII or ~150 s?1 mM ?1 per molecule of the final conjugate (20 MHz, 25 °C). In vitro labelling of pancreatic islets (PIs) and rat mesenchymal stem cells has been successfully performed. The agent is not cytotoxic and is easily internalized into cells. The labelled cells can be visualized by MRI, as proved by the detection of individual labelled PIs. A fluorescence study performed on mesenchymal stem cells showed that the agent stays in the intracellular space for a long time. 相似文献
A novel MRI contrast agent, hyaluronic acid gadolinium complex (HA‐Gd‐DTPA) nanospheres, is prepared by the synthesis of hyaluronic acid gadolinium complexes and their assembly. The physicochemical properties are characterized, and the lymphatic targeting in vitro and in vivo are also evaluated. The results show that the HA‐Gd‐DTPA nanospheres with suitable and stable physicochemical properties could be used for in vivo lymphatic targeting studies. Furthermore, the HA‐Gd‐DTPA nanospheres have obviously higher relaxation efficiency and MRI contrast between blood vessel and lymph vessel in rabbit than that of Magnevist. Thus, the novel MRI contrast agent can be taken up selectively by lymphatic system and used as a potential MRI contrast agents in lymphatic system. 相似文献
Homodinuclear lanthanide complexes (Ln=La, Eu, Gd, Tb, Yb and Lu) derived from a bis‐macrocyclic ligand featuring two 2,2′,2′′‐(1,4,7,10‐tetraazacyclododecane‐1,4,7‐triyl)triacetic acid chelating sites linked by a 2,6‐bis(pyrazol‐1‐yl)pyridine spacer (H2L3) were prepared and characterized. Luminescence lifetime measurements recorded on solutions of the EuIII and TbIII complexes indicate the presence of one inner‐sphere water molecule coordinated to each metal ion in these complexes. The overall luminescence quantum yields were determined (?=0.01 for [Eu2(L3)] and 0.50 for [Tb2(L3)] in 0.01 M TRIS/HCl, pH 7.4; TRIS=tris(hydroxymethyl)aminomethane), pointing to an effective sensitization of the metal ion by the bispyrazolylpyridyl unit of the ligand, especially with Tb. The nuclear magnetic relaxation dispersion (NMRD) profiles recorded for [Gd2(L3)] are characteristic of slowly tumbling systems, showing a low‐field plateau and a broad maximum around 30 MHz. This suggests the occurrence of aggregation of the complexes giving rise to slowly rotating species. A similar behavior is observed for the analogous GdIII complex containing a 4,4′‐dimethyl‐2,2′‐bipyridyl spacer ([Gd2(L1)]). The relaxivity of [Gd2(L3)] recorded at 0.5 T and 298 K (pH 6.9) amounts to 13.7 mM ?1 s?1. The formation of aggregates has been confirmed by dynamic light scattering (DLS) experiments, which provided mean particle sizes of 114 and 38 nm for [Gd2(L1)] and [Gd2(L3)], respectively. TEM images of [Gd2(L3)] indicate the formation of nearly spherical nanosized aggregates with a mean diameter of about 41 nm, together with some nonspherical particles with larger size. 相似文献
Glycosylation is a ubiquitous post‐translational modification, present in over 50 % of the proteins in the human genome, 1 with important roles in cell–cell communication and migration. Interest in glycome profiling has increased with the realization that glycans can be used as biomarkers of many diseases, 2 including cancer. 3 We report here the first tomographic imaging of glycosylated tissues in live mice by using metabolic labeling and a gadolinium‐based bioorthogonal MRI probe. Significant N‐azidoacetylgalactosamine dependent T1 contrast was observed in vivo two hours after probe administration. Tumor, kidney, and liver showed significant contrast, and several other tissues, including the pancreas, spleen, heart, and intestines, showed a very high contrast (>10‐fold). This approach has the potential to enable the rapid and non‐invasive magnetic resonance imaging of glycosylated tissues in vivo in preclinical models of disease. 相似文献
The novel amphipilic conjugate of a calix[4]arene with four Gd–1,4,7,10‐ tetra(carboxymethyl)‐1,4,7,10‐tetraazacyclododecane (DOTA) chelates has potential as a magnetic resonance imaging contrast agent, both in its monomeric and in its micellar form. The system, illustrated here with its nuclear magnetic relaxation profile, shows good relaxivities, thanks to its high rigidity.
Novel biodegradable dendritic contrast agents (DCAs) based on polyester dendrimers were synthesized and characterized.The DCAs were stable at acidic pH,but hydrolyzed rapidly at physiological pH,which rendered the DCA's long-term Gd3+ retention as low as that of small molecule CAs.Their longitudinal relaxivities of 10.2 to 17.5 L·mmol-1·s-1 were about 2.4 to 4.1 times higher than that of DTPA-Gd,indicating their superior contrast-enhancing capability to the clinically used contrast agent.The in vivo MRI study suggested that the DCA at lower generation (G2-DTPA-Gd) could effectively enhance the MRI of tumor,while the one at higher generation (G5-DTPA-Gd) showed more potential in liver imaging. 相似文献
Magneto‐plasmonic Janus vesicles (JVs) integrated with gold nanoparticles (AuNPs) and magnetic NPs (MNPs) were prepared asymmetrically in the membrane for in vivo cancer imaging. The hybrid JVs were produced by coassembling a mixture of hydrophobic MNPs, free amphiphilic block copolymers (BCPs), and AuNPs tethered with amphiphilic BCPs. Depending on the size and content of NPs, the JVs acquired spherical or hemispherical shapes. Among them, hemispherical JVs containing 50 nm AuNPs and 15 nm MNPs showed a strong absorption in the near‐infrared (NIR) window and enhanced the transverse relaxation (T2) contrast effect, as a result of the ordering and dense packing of AuNPs and MNPs in the membrane. The magneto‐plasmonic JVs were used as drug delivery vehicles, from which the release of a payload can be triggered by NIR light and the release rate can be modulated by a magnetic field. Moreover, the JVs were applied as imaging agents for in vivo bimodal photoacoustic (PA) and magnetic resonance (MR) imaging of tumors by intravenous injection. With an external magnetic field, the accumulation of the JVs in tumors was significantly increased, leading to a signal enhancement of approximately 2–3 times in the PA and MR imaging, compared with control groups without a magnetic field. 相似文献
Gadolinium‐based contrast agents (GBCAs) are used to provide diagnostic information in clinical magnetic resonance (MR) examinations. Gadolinium (Gd) has been detected in the brain, bone and skin of patients, months and years following GBCA administration, raising concerns about long term toxicity. Despite increased scrutiny, the concentration, chemical form and fate of the retained gadolinium species remain unknown. Importantly, the whole body biodistribution and organ clearance of GBCAs is poorly understood in humans. Gadolinium lacks suitable isotopes for nuclear imaging. We demonstrate that the yttrium‐86 isotope can be used as a gadolinium surrogate. We show that Gd and their analogous Y complexes have similar properties both in solution and in vivo, and that yttrium‐86 PET can be used to track the biodistribution of GBCAs over a two‐day period. 相似文献