Fluorescently Detectable Magnetic Resonance Imaging Agents

Hüber, Martina M.; Staubli, Andrea B.; Kustedjo, Karen; Gray, Mike H. B.; Shih, John; Fraser, Scott E.; Jacobs, Russell E.; Meade, Thomas J.

doi:10.1021/bc970153k

Cited by 187 publications

(159 citation statements)

References 18 publications

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“…The design of the final product, c: G6-(Bz-DTPA) 119 -(NIR) 4 -(Bz-DTPA-111In) 1 was rationally designed based on the need to develop a successful and easy-to-use dual-modal multicolor lymph node imaging agent. Bz-DTPA molecules were conjugated to more than half of the available surface amine residues on a dendrimer molecule for the following three reasons; 1. suppressing the poly-cation toxicity of dendrimer by changing the charge 15 , 2. facilitating efficient and stable 111 In-labeling to eventually enable this agent to be produced in a kit form by adding sufficient number of chelate molecules, 3.…”

Section: Resultsmentioning

confidence: 99%

“…DTPA solution at a final concentration of 0.2 mM was added to the radiolabeled products to complex potential free 111 In remaining in the product solution. The specific activities of all radiolabeled nano-probes were similar, ranging from 12.1 to 12.3 mCi/mg (c: G6-(Bz-DTPA) 119 -(NIR) 4 -(Bz-DTPA-111In) 1 in Figure 1). The radiolabeling yield of the radiolabeled nano-probes was >98% as determined by instant thin layer chromatography (ITLC; Gelman Sciences Ann Arbor, MI) developed with a solvent mixture containing 3:2:1 methanol:10% ammonium acetate in water:0.5 M citric acid and size-exclusion HPLC using a TSK G3000PWxL column (Tosoh Bioscience LLC, Montgomeryville, PA; 0.067 M PB-0.1 M KCl, pH 6.8; 1 ml/min).…”

Section: Radiolabeling With 111 Inmentioning

confidence: 95%

“…The concentrations of Cy5, Alexa660, 680, 700, and 750 were measured by their absorption at 651, 665, 681, 703, and 753 nm, respectively, using the UV-Vis system to confirm the number of fluorophore molecules conjugated with each G6 dendrimer molecule. The number of fluorophore molecules per G6-(Bz-DTPA) 120 was 4.1, 3.9, 3.6, 3.9, and 4.0 for Cy5, Alexa660, 680, 700, and 750, respectively (b: G6-(Bz-DTPA) 120 -(NIR) 4 in Figure 1). The yields of b were 91-93% for G6-(Bz-DTPA) 120 and 36-41% of NIR dye molecules were conjugated with G6-(Bz-DTPA) 120…”

Section: Conjugation Of Near Infrared Fluorescent Dyesmentioning

confidence: 99%

“…Dendrimers conjugated with NIR dyes (G6-(Bz-DTPA) 120 -(NIR) 4 ) were reacted with 111 In in 0.2 M sodium acetate buffer at pH 4.2 for 1 hr at room temperature, as previously described 32 . DTPA solution at a final concentration of 0.2 mM was added to the radiolabeled products to complex potential free 111 In remaining in the product solution.…”

Section: Radiolabeling With 111 Inmentioning

confidence: 99%

“…5 mg/300μL sodium pentobarbital (Dainabot, Osaka, Japan). The mice were administered intracutaneous injections of 10 μL/10 μCi (350 pmol for NIR dyes) of each G6-(Bz-DTPA) 119 -(NIR) 4 -(Bz-DTPA-111 In) 1 conjugate into one of 5 sites: the middle phalange of the left or right upper extremity, the left or right ear, and the median chin. For the first 5 consecutive mice only spectral fluorescence imaging was performed.…”

Section: In Vivo Multiple Excitation Wavelength-resolved 5-color Specmentioning

confidence: 99%

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Multimodal Nanoprobes for Radionuclide and Five-Color Near-Infrared Optical Lymphatic Imaging

et al. 2007

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Current contrast agents generally have one function and can only be imaged in monochrome, therefore, the majority of imaging methods can only impart uniparametric information. A single nano-particle has the potential to be loaded with multiple payloads. Such multi-modality probes have the ability to be imaged by more than one imaging technique, which could compensate for the weakness or even combine the advantages of each individual modality. Furthermore, optical imaging using different optical probes enables us to achieve multi-color in vivo imaging, wherein multiple parameters can be read from a single image. To allow differentiation of multiple optical signals in vivo, each probe should have a close but different near infrared emission. To this end, we synthesized nano-probes with multi-modal and multi-color potential, which employed a polyamidoamine dendrimer platform linked to both radionuclides and optical probes, permitting dual-modality scintigraphic and 5-color near infrared optical lymphatic imaging using a multiple excitation spectrally-resolved fluorescence imaging technique. Keywordsdendrimer; scintigraphy; near infrared; fluorescence imaging; multiple modalities; multiple colors; lymphatic imaging No imaging modality is perfect. Each has its own distinct advantages and limitations. The simultaneous use of two or more modalities can help to overcome the limitation of each individual method and increase or improve the information obtained during an examination session. The combined use of Computed Tomography (CT) and Positron Emission Tomography (PET) is a successful example of multi-modal imaging: CT provides high resolution anatomical detail and PET provides functional information 1 . Currently they are very few examples of multi-modal imaging probes that can be detected by more than one technique: dual agents for recognition by both radionuclide and optical imaging 2,3 , or Magnetic Resonance (MR) and optical imaging 4-8 . Furthermore, the conventional imaging methods are generally monochrome and only able to detect one contrast agent at a time, limiting us to single parametric data. Single photon scintigraphy has been shown to have potential for simultaneously detecting two different imaging agents, i.e. technetium-99m and thallium-201, by energy resolution 9 . However, in this case, both the spatial and the energy resolutions were poor and did not allow for the reconstruction of a precise image from each agent. Multi-color optical imaging is simple to achieve with the technique of spectrally resolved imaging. Herein, two or more optical agents can be differentiated on the basis of their different emission spectra. Multi-color imaging is already commonplace in microscopic imaging and is beginning to be utilized for in vivo imaging 10-12 . However, in vivo imaging is essentially limited to long wavelength dyes that emit in the near-infrared (NIR) range (650-850 nm), in order to maximize depth penetration and limit the autofluorescence, background signal 13 .With this in mind we have synthe...

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Section: Resultsmentioning

confidence: 99%

Section: Radiolabeling With 111 Inmentioning

confidence: 95%

Section: Conjugation Of Near Infrared Fluorescent Dyesmentioning

confidence: 99%

Section: Radiolabeling With 111 Inmentioning

confidence: 99%

Section: In Vivo Multiple Excitation Wavelength-resolved 5-color Specmentioning

confidence: 99%

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Multimodal Nanoprobes for Radionuclide and Five-Color Near-Infrared Optical Lymphatic Imaging

et al. 2007

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Medicinal Inorganic Chemistry: Ligand Design Objectives and Principles

Thompson

2005

Encyclopedia of Inorganic Chemistry

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Metal‐based pharmaceutical agents are composed of one or more metal ions and at least one ligand. Additional molecular substituents may include targeting moieties, linking groups, antioxidants, or pendant carbohydrates, or some combination of these. There are two main applications of metal‐based pharmaceutical agents: diagnostic and therapeutic. Ligand requirements for the two streams of development differ in some important ways, but are still based on the same basic principles for molecular design, including consideration of thermodynamic and hydrolytic stability, pharmacokinetics, molecular weight and charge, lipophilicity and hydrophilicity, aqueous solubility, functional groups, and ligand nontoxicity (sometimes achieved by using naturally occurring binding groups). Examples of the principles that are discussed in this article include Gd(III)‐based magnetic resonance imaging (MRI) contrast agents, Cu(II)‐clotrimazole, proposed as an antiparasitic agent, 67 Ga‐citrate for tumor imaging, and 99 m Tc(I)‐sestamibi for cardiac imaging.

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