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In vivo evaluation of the dopaminergic neurotransmission system using [123I]FP‐CIT SPECT in 6‐OHDA lesioned rats
The 6‐hydroxydopamine (6‐OHDA) rodent model of Parkinson's disease (PD) has been used to evaluate the nigrostriatal pathway. The aim of this work was to explore the relationship between the degree of 6‐OHDA‐induced dopaminergic degeneration and [123I]FP‐CIT binding using single photon emission computed tomography (SPECT). Fourteen rats received a 6‐OHDA injection (4 or 8 µg) into the left medial forebrain bundle. After 3 weeks, magnetic resonance imaging and scans with a small‐animal SPECT system were performed. Finally, the nigrostriatal lesion was assessed by immunohistochemical analysis. Immunohistoch...
Source: Contrast Media and Molecular Imaging - May 28, 2014 Category: Radiology Authors: Aida Niñerola‐Baizán, Santiago Rojas, Mercè Bonastre, Raúl Tudela, Francisco Lomeña, Javier Pavía, Concepció Marin, Domènec Ros Tags: Full Paper Source Type: research

In vivo biodistribution of radiolabeled MMP‐2/9 activatable cell‐penetrating peptide probes in tumor‐bearing mice
In conclusion, this study suggests that tumoral ACPP uptake in these tumor models originates from probe activation in the vasculature instead of tumor‐specific MMP activation. Novel ACPPs that target tissue‐specific proteases without nonspecific activation may unleash the full potential of the elegant ACPP concept. Copyright © 2014 John Wiley & Sons, Ltd.We present the in vivo biodistribution of matrix metalloproteinase activatable cell‐penetrating imaging probes (ACPP) in mice bearing subcutaneous HT‐1080 tumors with high MMP expression, and in control mice bearing subcutaneous BT‐20 tumors with low MMP exp...
Source: Contrast Media and Molecular Imaging - May 14, 2014 Category: Radiology Authors: Sander M. J. Duijnhoven, Marc S. Robillard, Klaas Nicolay, Holger Grüll Tags: Full Paper Source Type: research

Lanthanide ion (III) complexes of 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraaminophosphonate for dual biosensing of pH with chemical exchange saturation transfer (CEST) and biosensor imaging of redundant deviation in shifts (BIRDS)
Relaxivity‐based magnetic resonance of phosphonated ligands chelated with gadolinium (Gd3+) shows promise for pH imaging. However instead of monitoring the paramagnetic effect of lanthanide complexes on the relaxivity of water protons, biosensor (or molecular) imaging with magnetic resonance is also possible by detecting either the nonexchangeable or the exchangeable protons on the lanthanide complexes themselves. The nonexchangeable protons (e.g. –CHx, where 3 ≥ x ≥ 1) are detected using a three‐dimensional chemical shift imaging method called biosensor imaging of redundant deviation in shifts (BIRDS), w...
Source: Contrast Media and Molecular Imaging - May 8, 2014 Category: Radiology Authors: Yuegao Huang, Daniel Coman, Meser M. Ali, Fahmeed Hyder Tags: Full Paper Source Type: research

Gallium(III) complexes of NOTA‐bis (phosphonate) conjugates as PET radiotracers for bone imaging
Ligands with geminal bis(phosphonic acid) appended to 1,4,7‐triazacyclonone‐1,4‐diacetic acid fragment through acetamide (NOTAMBP) or methylenephosphinate (NO2APBP) spacers designed for 68Ga were prepared. GaIII complexation is much faster for ligand with methylenephosphinate spacer than that with acetamide one, in both chemical (high reactant concentrations) and radiolabeling studies with no‐carrier‐added 68Ga. For both ligands, formation of GaIII complex was slower than that with NOTA owing to the strong out‐of‐cage binding of bis(phosphonate) group. Radiolabeling was efficient and fast only above 60 °C an...
Source: Contrast Media and Molecular Imaging - May 6, 2014 Category: Radiology Authors: Jan Holub, Marian Meckel, Vojtěch Kubíček, Frank Rösch, Petr Hermann Tags: Full Paper Source Type: research

Anthranilic acid analogs as diamagnetic CEST MRI contrast agents that feature an intramolecular‐bond shifted hydrogen
Diamagnetic chemical exchange saturation transfer (diaCEST) agents are a new class of imaging agents, which have unique magnetic resonance (MR) properties similar to agents used for optical imaging. Here we present a series of anthranilic acid analogs as examples of diaCEST agents that feature an exchangeable proton shifted downfield, namely, an intramolecular‐bond shifted hydrogen (IM‐SHY), which produces significant and tunable contrast at frequencies of 4.8–9.3 ppm from water. Five analogs of N‐sulfonyl anthranilic acids are all highly soluble and produced similar CEST contrast at ~6–8 ppm. We also discovered ...
Source: Contrast Media and Molecular Imaging - April 28, 2014 Category: Radiology Authors: Xiaolei Song, Xing Yang, Sangeeta Ray Banerjee, Martin G. Pomper, Michael T. McMahon Tags: Short Communication Source Type: research

Relaxivity enhancement of aquated Tris(β‐diketonate)gadolinium(III) chelates by confinement within ultrashort single‐walled carbon nanotubes
Ultrashort single‐walled carbon nanotubes loaded with gadolinium ions (gadonanotubes) have been previously shown to exhibit extremely high T1‐weighted relaxivities (>100 mm−1 s−1). To further examine the effect of nanoconfinement on the relaxivity of gadolinium‐based contrast agents for magnetic resonance imaging, a series of ultrashort single‐walled carbon nanotube (US‐tube) materials internally loaded with gadolinium chelates have been prepared and studied. US‐tubes were loaded with Gd(acac)3 · 2H2O, Gd(hfac)3 · 2H2O, and Gd(thd)3 (acac = acetylacetone, hfac = hexafluoroacetylacetone,...
Source: Contrast Media and Molecular Imaging - April 26, 2014 Category: Radiology Authors: Justin J. Law, Adem Guven, Lon J. Wilson Tags: Short Communication Source Type: research

Targeting human prostate cancer with 111In‐labeled D2B IgG, F(ab′)2 and Fab fragments in nude mice with PSMA‐expressing xenografts
This study demonstrates the feasibility of D2B IgG, F(ab′)2 and Fab fragments for targeting PSMA‐expressing prostate cancer xenografts. Copyright © 2014 John Wiley & Sons, Ltd. The potential of the 111In‐labeled anti‐PSMA antibody D2B IgG, F(ab′)2 and Fab fragments for targeting prostate cancer was determined in mice with subcutaneous PSMA‐expressing prostate cancer xenografts. The PSMA‐expressing xenografts were clearly visualized with SPECT/CT. Highest accumulation in the tumor lesions was observed with 111In‐D2B IgG (94.8 ± 19.2% ID/g at 168 h p.i.). Renal accumulation of F(ab′)2 and Fab fr...
Source: Contrast Media and Molecular Imaging - April 25, 2014 Category: Radiology Authors: Susanne Lütje, Catharina M. Rij, Gerben M. Franssen, Giulio Fracasso, Wijnand Helfrich, Annemarie Eek, Wim J. Oyen, Marco Colombatti, Otto C. Boerman Tags: Full Paper Source Type: research

Disruptive chemical doping in a ferritin‐based iron oxide nanoparticle to decrease r2 and enhance detection with T1‐weighted MRI
Inorganic doping was used to create flexible, paramagnetic nanoparticle contrast agents for in vivo molecular magnetic resonance imaging (MRI) with low transverse relaxivity (r2). Most nanoparticle contrast agents formed from superparamagnetic metal oxides are developed with high r2. While sensitive, they can have limited in vivo detection due to a number of constraints with T2 or T2*‐weighted imaging. T1‐weighted imaging is often preferred for molecular MRI, but most T1‐shortening agents are small chelates with low metal payload or are nanoparticles that also shorten T2 and limit the range of concentrations detectab...
Source: Contrast Media and Molecular Imaging - April 25, 2014 Category: Radiology Authors: M. Veronica Clavijo Jordan, Scott C. Beeman, Edwin J. Baldelomar, Kevin M. Bennett Tags: Full Paper Source Type: research

Three‐dimensional imaging of the mouse heart and vasculature using micro‐CT and whole‐body perfusion of iodine or phosphotungstic acid
This study describes a perfusion approach using iodine or phosphotungstic acid (PTA) stains, delivered to an intact mouse, to capitalize on the microvasculature as a delivery conduit for parenchymal staining and direct contact for staining artery walls. Twelve C57BL/6 mice, arterially perfused with either 25% Lugol's solution or 5% PTA solution were scanned intact and reconstructed with 26 µm isotropic voxels. The animals were fixed and the heart and surrounding vessels were excised, embedded and scanned; isolated heart images were reconstructed with 13 µm isotropic voxels. Myocardial enhancement and artery diameters...
Source: Contrast Media and Molecular Imaging - April 25, 2014 Category: Radiology Authors: P. Joy Dunmore‐Buyze, Elsbeth Tate, Fu‐li Xiang, Sarah A. Detombe, Zengxuan Nong, J. Geoffrey Pickering, Maria Drangova Tags: Full Paper Source Type: research

In vivo quantification of SPIO nanoparticles for cell labeling based on MR phase gradient images
Along with the development of modern imaging technologies, contrast agents play increasingly important roles in both clinical applications and scientific research. Super‐paramagnetic iron oxide (SPIO) nanoparticles, a negative contrast agent, have been extensively used in magnetic resonance imaging (MRI), such as in vivo labeling and tracking of cells. However, there still remain many challenges, such as in vivo quantification of SPIO nanoparticles. In this work, an MR phase gradient‐based method was proposed to quantify the SPIO nanoparticles. As a calibration, a phantom experiment using known concentrations (10, 25, ...
Source: Contrast Media and Molecular Imaging - April 25, 2014 Category: Radiology Authors: Luning Wang, William M. Potter, Qun Zhao Tags: Full Paper Source Type: research

Minimization of self‐quenching fluorescence on dyes conjugated to biomolecules with multiple labeling sites via asymmetrically charged NIR fluorophores
Self‐aggregation of dyes even at low concentrations poses a considerable challenge in preparing sufficiently bright molecular probes for in vivo imaging, particularly in the conjugation of near infrared cyanine dyes to polypeptides with multiple labeling sites. Such self‐aggregation leads to a significant energy transfer between the dyes, resulting in severe quenching and low brightness of the targeted probe. To address this problem, we designed a novel type of dye with an asymmetrical distribution of charge. Asymmetrical distribution prevents the chromophores from π‐stacking thus minimizing the energy transfer and ...
Source: Contrast Media and Molecular Imaging - April 25, 2014 Category: Radiology Authors: Natalia G. Zhegalova, Shawn He, Haiying Zhou, David M. Kim, Mikhail Y. Berezin Tags: Full Paper Source Type: research

Entrapment of a neutral Tm(III)‐based complex with two inner‐sphere coordinated water molecules into PEG‐stabilized vesicles: towards an alternative strategy to develop high‐performance LipoCEST contrast agents for MR imaging
Chemical exchange saturation transfer (CEST) probes issued from the encapsulation of a water proton paramagnetic shift reagent into the inner aqueous volume of lipid vesicles provide an emerging class of frequency‐selective contrast agents with huge potential in the field of molecular magnetic resonance imaging (MRI). This work deals with the generation of such LipoCEST agents properly designed to optimize, under isotonic conditions, the chemical shift offset of the intra‐liposomal water protons as well as the number of exchangeable protons under reasonably low radiofrequency (RF) fields of saturation. The strategy lie...
Source: Contrast Media and Molecular Imaging - April 24, 2014 Category: Radiology Authors: Bochra Chahid, Luce Vander Elst, Julien Flament, Fawzi Boumezbeur, Christelle Medina, Marc Port, Robert N. Muller, Sylviane Lesieur Tags: Full Paper Source Type: research

Multimodal imaging of micron‐sized iron oxide particles following in vitro and in vivo uptake by stem cells: down to the nanometer scale
In this study, the interaction between cells and micron‐sized paramagnetic iron oxide (MPIO) particles was investigated by characterizing MPIO in their original state, and after cellular uptake in vitro as well as in vivo. Moreover, MPIO in the olfactory bulb were studied 9 months after injection. Using various imaging techniques, cell–MPIO interactions were investigated with increasing spatial resolution. Live cell confocal microscopy demonstrated that MPIO co‐localize with lysosomes after in vitro cellular uptake. In more detail, a membrane surrounding the MPIO was observed by high‐angle annular dark‐field sc...
Source: Contrast Media and Molecular Imaging - April 22, 2014 Category: Radiology Authors: Dimitri Roose, Frederic Leroux, Nathalie De Vocht, Caroline Guglielmetti, Isabel Pintelon, Dirk Adriaensen, Peter Ponsaerts, Annemie Van der Linden, Sara Bals Tags: Full Paper Source Type: research

Sub‐second proton imaging of 13C hyperpolarized contrast agents in water
Indirect proton detection of 13C hyperpolarized contrast agents potentially enables greater sensitivity. Presented here is a study of sub‐second projection imaging of hyperpolarized 13C contrast agent addressing the obstacle posed by water suppression for indirect detection in vivo. Sodium acetate phantoms were used to develop and test water suppression and sub‐second imaging with frequency‐selective RF pulses using spectroscopic and imaging indirect proton detection. A 9.8 mm aqueous solution of 13C PHIP hyperpolarized 2‐hydroxyethyl‐13C‐propionate‐d2,3,3 (HEP), <P > ~25% was used for demonstrati...
Source: Contrast Media and Molecular Imaging - April 22, 2014 Category: Radiology Authors: Milton L. Truong, Aaron M. Coffey, Roman V. Shchepin, Kevin W. Waddell, Eduard Y. Chekmenev Tags: Full Paper Source Type: research

Glycolaldehyde and maleyl conjugated human serum albumin as potential macrophage‐targeting carriers for molecular imaging purposes
We present a novel synthesis of glycolaldehyde‐conjugated human serum albumin (GA‐HSA) and maleylated human serum albumin (Mal‐HSA). Seventeen modifications of fluorescently tagged GA‐HSA and Mal‐HSA molecules with different degrees of conjugation were prepared. The comparative uptake studies, using 12 of these modifications, were done in vitro on mouse monocytes/macrophages (RAW264.7), and evaluated qualitatively by confocal microscopy and quantitatively by flow cytometry. The GA modifications are taken up by the macrophages approximately 40% better than the maleyl modifications at low concentrations (≤3 μm),...
Source: Contrast Media and Molecular Imaging - April 21, 2014 Category: Radiology Authors: Björn Gustafsson, Ulf Hedin, Kenneth Caidahl Tags: Full Paper Source Type: research