Contrast Media & Molecular Imaging

Cover image for Contrast Media & Molecular Imaging

March/April 2012

Volume 7, Issue 2

Pages 130–279, i–iii

  1. Issue Information

    1. Top of page
    2. Issue Information
    3. Abstracts
    4. Full Papers
    5. Short Communication
    1. Issue Information (pages i–iii)

      Article first published online: 20 MAR 2012 | DOI: 10.1002/cmmi.1471

  2. Abstracts

    1. Top of page
    2. Issue Information
    3. Abstracts
    4. Full Papers
    5. Short Communication
  3. Full Papers

    1. Top of page
    2. Issue Information
    3. Abstracts
    4. Full Papers
    5. Short Communication
    1. Intracellular SPIO labeling of microglia: high field considerations and limitations for MR microscopy (pages 121–129)

      Jens T. Rosenberg, Afi Sachi-Kocher, Michael W. Davidson and Samuel C. Grant

      Article first published online: 14 MAR 2012 | DOI: 10.1002/cmmi.470

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      To evaluate superparamagnetic iron oxides (SPIOs) at ultra-high magnetic fields, microglia cells were transfected for analysis at 11.75 and 21.1 T. Viability was unaffected by SPIOs and showed a linear uptake with exposure. Though displaying no field-dependent benefits for T1 and T2, intracellular SPIOs showed enhanced T2* contrast at 21.1 T. Iron content and cell count measurements were not enhanced at 21.1 T. Therefore, the detectability of SPIO-labeled cells at high fields is significant but quantifiable metrics are more limited.

    2. Efficacy of positive contrast imaging techniques for molecular MRI of tumor angiogenesis (pages 130–139)

      M. Wolters, M. Oostendorp, B. F. Coolen, M. J. Post, J. M. H. Janssen, G. J. Strijkers, M. E. Kooi, K. Nicolay and W. H. Backes

      Article first published online: 6 MAR 2012 | DOI: 10.1002/cmmi.471

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      This study evaluates positive contrast techniques, i.e. white marker and susceptibility gradient mapping (SGM), for molecular MRI with cNGR-labeled SPIOs to selectively detect tumor angiogenesis in mice. Only SGM, and not white marker, can be used to transfer the negative contrast in GE images (arrows) from targeted SPIOs in positive contrast (arrows in SGM image) without loss of contrast-to-noise ratio compared with negative contrast in GE images.

    3. Limitations and caveats of magnetic cell labeling using transfection agent complexed iron oxide nanoparticles (pages 140–152)

      Stefaan J. Soenen, Stefaan C. De Smedt and Kevin Braeckmans

      Article first published online: 14 MAR 2012 | DOI: 10.1002/cmmi.472

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      For efficient magnetic cell labeling, the iron oxide nanoparticles are frequently complexed with cationic transfection agents such as Lipofectamine, but the effect thereof remains unclear. In the present work, it is shown that higher ratios of Lipofectamine over dextran-coated particles induce severe aggregation, lead to cell-surface adsorption of the complexes with lower cellular uptake and alter the lysosomal structure due to intraendosomal presence of large aggregates. At lower ratios, the complexes are better internalized through multiple endocytic mechanisms.

    4. Functionalized single-walled carbon nanotubes containing traces of iron as new negative MRI contrast agents for in vivo imaging (pages 153–159)

      Bich-Thuy Doan, Johanne Seguin, Marie Breton, Ronan Le Beherec, Michel Bessodes, Julio A. Rodríguez-Manzo, Florian Banhart, Jean-Claude Beloeil, Daniel Scherman and Cyrille Richard

      Article first published online: 14 MAR 2012 | DOI: 10.1002/cmmi.474

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      Single-walled carbon nanotubes containing traces of iron were functionalized to supply new efficient MRI contrast agents for in vitro and in vivo applications. Longitudinal (r1) and transversal (r2) water proton relaxivities were measured at 300 MHz showing a stronger T2 feature as an MRI contrast agent (r2/r1 = 190). Biodistribution studies on mice after a systemic injection showed a negative contrast in liver.

    5. Radiolabelled GLP-1 analogues for in vivo targeting of insulinomas (pages 160–166)

      Maarten Brom, Lieke Joosten, Wim J. G. Oyen, Martin Gotthardt and Otto C. Boerman

      Article first published online: 6 MAR 2012 | DOI: 10.1002/cmmi.475

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      The GLP-1R agonists Exendin-3 and Exendin-4 show high receptor affinity and efficient in vitro binding and internalization kinetics. [Lys40(111In-DTPA)]Exendin-3 and [Lys40(111In-DTPA)]Exendin-4 accumulated efficiently in GLP-1R positive INS-1 tumours and GLP-1R positive organs and could therefore be useful for detection and therapy of insulinomas. [Lys40(DTPA)]Exendin(9-39) exhibited high affinity for the GLP-1R, but did not show internalization and low uptake in INS-1 tumours and GLP-1R positive organs and therefore is not suited for targeting the GLP-1R in vivo.

    6. Improved quantification in pinhole gated myocardial perfusion SPECT using micro-CT and ultrasound information (pages 167–174)

      Lode R. Goethals, Frank De Geeter, Chris Vanhove, Bram Roosens, Hannes Devos and Tony Lahoutte

      Article first published online: 14 MAR 2012 | DOI: 10.1002/cmmi.477

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      Absolute quantification using SPECT has been demonstrated in vitro and in large immobile organs in vivo. Using an ultrasound derived partial volume effect correction factor combined with attenuation and scatter correction in gated acquisitions, an improved quantification is feasible in myocardial perfusion SPECT.

    7. Novel Gd(III)-based probes for MR molecular imaging of matrix metalloproteinases (pages 175–184)

      Concetta V. Gringeri, Valeria Menchise, Silvia Rizzitelli, Evelina Cittadino, Valeria Catanzaro, Gabriele Dati, Linda Chaabane, Giuseppe Digilio and Silvio Aime

      Article first published online: 14 MAR 2012 | DOI: 10.1002/cmmi.478

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      An MRI approach for the visualization of matrix metalloproteinase activity based upon an MMP-cleavable gadolinium-based contrast agent is presented. As a consequence of enzymatic cleavage, the CA undergoes an amphiphilic-to-hydrophilic transformation, leading to an alteration of the pharmacokinetic profile. Washout kinetics of Gd-contrast enhancement from the tumor can then be related to the local activity of MMPs.

    8. Polyglycerol-grafted superparamagnetic iron oxide nanoparticles: highly efficient MRI contrast agent for liver and kidney imaging and potential scaffold for cellular and molecular imaging (pages 185–194)

      Nasser Arsalani, Hassan Fattahi, Sophie Laurent, Carmen Burtea, Luce Vander Elst and Robert N. Muller

      Article first published online: 14 MAR 2012 | DOI: 10.1002/cmmi.479

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      Highly stable water-based ferrofluid was prepared by covalently grafting of hyperbranched polyglycerol as a water-soluble and biocompatible polymer on the surface of superparamagnetic iron oxide nanoparticles. Calculated r1 and r2 relaxivities at different magnetic fields and also in vivo MRI studies on mice show its high potential as an MRI contrast agent for the diagnosis of liver and kidney lesions, avoiding the drawback of organ retention and the subsequent toxicity.

    9. Cell quantification: evolution of compartmentalization and distribution of iron-oxide particles and labeled cells (pages 195–203)

      Gyula Kotek, Sandra T. van Tiel, Piotr A. Wielopolski, Gavin C. Houston, Gabriel P. Krestin and Monique R. Bernsen

      Article first published online: 6 MAR 2012 | DOI: 10.1002/cmmi.481

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      In our study we show the feasibility and the limitations of cell quantification by parametric MRI in the case of cell death, cell migration and cell division. We demonstrate that relaxometry does not allow labeled cell quantification when multiple physiological processes such as cell division and cell migration coexist. However, quantification of the number of labeled cells by relaxometry seems feasible under special circumstances.

    10. An approach towards molecular imaging of activated platelets allows imaging of symptomatic human carotid plaques in a new model of a tissue flow chamber (pages 204–213)

      Dominik von Elverfeldt, Mirko Meißner, Karlheinz Peter, Dominik Paul, Fabian Meixner, Irene Neudorfer, Annette Merkle, Andreas Harloff, Andreas Zirlik, Joachim Schöllhorn, Michael Markl, Jürgen Hennig, Christoph Bode and Constantin von zur Muhlen

      Article first published online: 14 MAR 2012 | DOI: 10.1002/cmmi.482

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      We established molecular MRI of human endarterectomy specimes, allowing detection of activated platelets on the surface of symptomatic plaques by using a platelet-specific contrast agent in a newly constructed setup of an MRI tissue flow chamber, simulating physiological flow conditions inside the specimen. As a perspective, the flow chamber approach described in this study could help to evaluate binding properties of contrast agents, which seem to qualify for human applications after successful use in animal studies, and might therefore be an interesting tool for contrast agent development towards its clinical application.

    11. Dual-isotope 111In/177Lu SPECT imaging as a tool in molecular imaging tracer design (pages 214–222)

      Nicole M Hijnen, Anke de Vries, Klaas Nicolay and Holger Grüll

      Article first published online: 14 MAR 2012 | DOI: 10.1002/cmmi.485

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      New molecular imaging tracers can be tested on their in vivo net targeting specificity by utilizing quantitative dual-isotope SPECT imaging. This study demonstrates this tracer design tool for simultaneously injected 111In/177Lu labeled cRGDfK-DOTA and cRADfK-DOTA.

    12. A radiolabeled nonapeptide probe targeting PC-3 cells and bone metastases of prostate cancer in mice (pages 223–230)

      Wu Qinghua, Xu Jianli, Liu Lu, Yang Zexuan, Tong Guansheng, Gao Hailin and Jiang Jianwei

      Article first published online: 6 MAR 2012 | DOI: 10.1002/cmmi.486

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      The comparison between 99mTc-MDP imaging and 99mTc-DTPA-c(CGRRAGGSC) imaging in normal nude mouse and the tumor-bearing mouse at 4 h after tail vein administration. Competitive inhibition experiment in vivo showed no obvious radioactive intake in normal tissues. Three weeks later, X-ray films showed bone destruction with tumor tissue imaging in the tumor in the lower femur.

    13. Optimized synthesis of 100 nm diameter magnetoliposomes with high content of maghemite particles and high MRI effect (pages 231–239)

      Boris Garnier, Sisareuth Tan, Sylvain Miraux, Emilie Bled and Alain R. Brisson

      Article first published online: 6 MAR 2012 | DOI: 10.1002/cmmi.487

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      Magnetoliposomes were produced by hydration of a lipid film with citrate-coated iron oxide particles, followed by extrusion. The synthesis procedure was optimized to produce magnetoliposomes of small size −100-nm in diameter-, with a maximal iron content -up to 77 maghemite particles/liposome, equivalent to 5.6 mol iron per mol lipid-, and a high r2 MRI relaxivity -up to 320 mM−1.s−1. This work demonstrates that creating a high local particle concentration inside the liposome reservoir enhances the MRI contrast.

    14. Evaluation of eXIA 160XL cardiac-related enhancement in C57BL/6 and BALB/c mice using micro-CT (pages 240–246)

      Sarah A. Detombe, Joy Dunmore-Buyze and Maria Drangova

      Article first published online: 14 MAR 2012 | DOI: 10.1002/cmmi.488

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      This study evaluated the blood-pool enhancement time-course of eXIA 160XL to determine its optimal use during cardiac function studies in mice. In both C57BL/6 and BALB/c strains, this contrast agent provided high contrast between blood and myocardial tissue for a period of 30 minutes following injection. Notably, this contrast agent was also taken up by the myocardium and provided continued enhancement when it was eliminated from the blood, making LV wall motion studies possible. With its high iodine concentration and targeted tissue uptake characteristics, eXIA 160XL is an ideal agent to use when evaluating cardiovascular function in mice.

    15. MR and optical imaging of early micrometastases in lymph nodes: triple labeling with nano-sized agents yielding distinct signals (pages 247–253)

      Nobuyuki Kosaka, Marcelino Bernardo, Makoto Mitsunaga, Peter L. Choyke and Hisataka Kobayashi

      Article first published online: 14 MAR 2012 | DOI: 10.1002/cmmi.489

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      The simultaneous use of negative contrast agent (SPIO) for the cancer cells and a positive MR contrast agent (Gd-G6) for the lymphangiography enables clear visualization of early micrometastases within the nodes, while additional labeling with QD provides high spatial resolution confirmation of the migrated cancer cells on intravital surgical microscopy in real time.

    16. Development of 177Lu-nanobodies for radioimmunotherapy of HER2-positive breast cancer: evaluation of different bifunctional chelators (pages 254–264)

      Matthias D'Huyvetter, An Aerts, Catarina Xavier, Ilse Vaneycken, Nick Devoogdt, Marlies Gijs, Nathalie Impens, Sarah Baatout, Bernard Ponsard, Serge Muyldermans, Vicky Caveliers and Tony Lahoutte

      Article first published online: 20 MAR 2012 | DOI: 10.1002/cmmi.491

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      In this paper we compared different bifunctional chelators – p-SCN-Bn-DOTA, DOTA-NHS-ester, CHX-A′′-DTPA or 1B4M-DTPA – to select the optimal chemical link between the therapeutic radionuclide Lutetium-177 and the anti-HER2 nanobody 2Rs15dHIS. We observed that the nanobody can be successfully labeled with 177Lu without quantitatively affecting antigen recognition. Both macrocyclic and acyclic chelators show high stability in time. High and sustained tumor uptake until 48 h post-injection combined with the lowest uptake in healthy tissues was measured for the 1B4M-DTPA-based conjugate.

    17. Mn-alginate gels as a novel system for controlled release of Mn2+ in manganese-enhanced MRI (pages 265–275)

      Ýrr A. Mørch, Ioanna Sandvig, Øystein Olsen, Ivan Donati, Marte Thuen, Gudmund Skjåk-Bræk, Olav Haraldseth and Christian Brekken

      Article first published online: 14 MAR 2012 | DOI: 10.1002/cmmi.493

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      Biopolymer gels are here used as a novel system for the controlled release of manganese ions for application in manganese-enhanced MRI (MEMRI). Our findings demonstrate the possibility to circumvent the challenge of achieving optimal MRI resolution without resorting to high, potentially cytotoxic doses of Mn2+.

  4. Short Communication

    1. Top of page
    2. Issue Information
    3. Abstracts
    4. Full Papers
    5. Short Communication
    1. 1H chemical shift magnetic resonance imaging probes with high sensitivity for multiplex imaging (pages 276–279)

      Yan Yang, Daniel T. Schühle, Guangping Dai, Jamu K. Alford and Peter Caravan

      Article first published online: 14 MAR 2012 | DOI: 10.1002/cmmi.490

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      Simultaneous imaging of different 1H chemical shift reporters results in multiplexed detection by chemical shift imaging. Encapsulation of these reporters inside nano-carriers yields systems capable of delivering high payloads to targets. Co-encapsulation with a relaxation agent results in improved sensitivity and suppresses background signals.

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