Nanomedicine: Perspective and promises with ligand-directed molecular imaging

Pan, Dipanjan; Lanza, Gregory M.; Wickline, Samuel A.; Caruthers, Shelton D.

doi:10.1016/j.ejrad.2009.01.042

Cited by 95 publications

(109 citation statements)

References 192 publications

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“…1 H MRI CNR vs nanoparticle concentration resulted in different linear slopes for RGD-and NT-emulsions, prohibiting unambiguous quantification of nanoparticle concentration. Nevertheless, the high CNR and low detection threshold enable high-resolution in vivo imaging of nanoparticle distributions in an anatomical context as has been demonstrated in various previous studies (32,33). 19 F MRI yielded linear CNR with nanoparticle concentration, which demonstrates that fluorine imaging is quantitative even in the situation when nanoparticles are internalized into cells and exposed to the rather hostile environment of the intracellular space.…”

mentioning

confidence: 64%

Quantitative ¹H MRI, ¹⁹F MRI, and ¹⁹F MRS of cell‐internalized perfluorocarbon paramagnetic nanoparticles

Kok¹,

Vries²,

Abdurrachim³

et al. 2011

Contrast Media & Molecular

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In vivo molecular imaging with targeted MRI contrast agents will require sensitive methods to quantify local concentrations of contrast agent, enabling not only imaging-based recognition of pathological biomarkers but also detection of changes in expression levels as a consequence of disease development, therapeutic interventions or recurrence of disease. In recent years, targeted paramagnetic perfluorocarbon emulsions have been frequently applied in this context, permitting high-resolution (1)H MRI combined with quantitative (19)F MR imaging or spectroscopy, under the assumption that the fluorine signal is not altered by the local tissue and cellular environment. In this in vitro study we have investigated the (19)F MR-based quantification potential of a paramagnetic perfluorocarbon emulsion conjugated with RGD-peptide to target the cell-internalizing α(ν)β(3)-integrin expressed on endothelial cells, using a combination of (1)H MRI, (19)F MRI and (19)F MRS. The cells took up the targeted emulsion to a greater extent than nontargeted emulsion. The targeted emulsion was internalized into large 1-7 µm diameter vesicles in the perinuclear region, whereas nontargeted emulsion ended up in 1-4 µm diameter vesicles, which were more evenly distributed in the cytoplasm. Association of the targeted emulsion with the cells resulted in different proton longitudinal relaxivity values, r(1), for targeted and control nanoparticles, prohibiting unambiguous quantification of local contrast agent concentration. Upon cellular association, the fluorine R(1) was constant with concentration, while the fluorine R(2) increased nonlinearly with concentration. Even though the fluorine relaxation rate was not constant, the (19)F MRI and (19)F MRS signals for both targeted nanoparticles and controls were linear and quantifiable as function of nanoparticle concentration.

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mentioning

confidence: 64%

Quantitative ¹H MRI, ¹⁹F MRI, and ¹⁹F MRS of cell‐internalized perfluorocarbon paramagnetic nanoparticles

Kok¹,

Vries²,

Abdurrachim³

et al. 2011

Contrast Media & Molecular

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“…Additionally, luteinizing hormone-releasing hormone (LHRH) conjugated USPIOs have been shown to enhance MRI and microscopy of LHRH receptor-expressing breast cancers (and their lung metastases) in mouse models [12]. These supermagnetic nanoparticles have also been conjugated with antibodies against HER2, which potentially enables simultaneous imaging and therapy of breast cancer [2,11,14].…”

Section: Imagingmentioning

confidence: 99%

“…This is a tumor-targeting mechanism known as enhanced permeation and retention (EPR) [1,14,15]. By adding polyethylene glycol to the vector, clearance from the system is prolonged [4,[13][14][15]. Liposomal doxorubicin and pegylated liposomal doxorubicin have been compared with conventional (systemic) doxorubicin in first-line treatment of patients with metastatic breast cancer.…”

Section: Drug Deliverymentioning

confidence: 99%

Impact of nanotechnology in breast cancer

Haq

Zabkiewicz

Grange

et al. 2009

Expert Review of Anticancer Therapy

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“…Moreover, combining the more recent nuclear imaging multimodalities, which provide high sensitivity and anatomical resolution such as PET/CT and SPECT/CT, with the use of specific tumor-targeting radiopharmaceuticals, constitutes a promising strategy that will allow for earlier tumor detection, better treatment planning and more effective therapy, in the near future (Jain, Patravale, 2009;Pan et al, 2009;Hamoudeh et al, 2008).…”

Section: Polymeric Micelles For Diagnosis and Cancer Therapymentioning

confidence: 99%

“…The use of new molecules, radiopharmaceuticals or contrast agents, allied to traditional imaging tools, has enabled visualization of tissular events and disclosure of the specific molecular targets in the body which are S. R. M. Grallert, C. O. Rangel-Yagui, K. F. M. Pasqualoto, L. C. Tavares 2 responses during disease progression (Pan et al, 2009;Wong, Kim, 2009).…”

Section: Introductionmentioning

confidence: 99%

Polymeric micelles and molecular modeling applied to the development of radiopharmaceuticals

Grallert

Rangel-Yagui

Pasqualoto

et al. 2012

Braz. J. Pharm. Sci.

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Micelles composed of amphiphilic copolymers linked to a radioactive element are used in nuclear medicine predominantly as a diagnostic application. A relevant advantage of polymeric micelles in aqueous solution is their resulting particle size, which can vary from 10 to 100 nm in diameter. In this review, polymeric micelles labeled with radioisotopes including technetium (99mTc) and indium (111In), and their clinical applications for several diagnostic techniques, such as single photon emission computed tomography (SPECT), gamma-scintigraphy, and nuclear magnetic resonance (NMR), were discussed. Also, micelle use primarily for the diagnosis of lymphatic ducts and sentinel lymph nodes received special attention. Notably, the employment of these diagnostic techniques can be considered a significant tool for functionally exploring body systems as well as investigating molecular pathways involved in the disease process. The use of molecular modeling methodologies and computer-aided drug design strategies can also yield valuable information for the rational design and development of novel radiopharmaceuticals.
Micelas poliméricas compostas de copolímeros ligadas a um elemento radioativo são utilizadas em Medicina Nuclear com aplicação predominantemente diagnóstica. A vantagem relevante da utilização de micelas poliméricas em solução aquosa é o tamanho de suas partículas, as quais podem variar de 10 a 100 nm de diâmetro. Neste trabalho de revisão são apresentadas micelas poliméricas marcadas com radioisotopos, como tecnécio-99m (99mTc) e índio-111 (111In), assim como suas aplicações clínicas em técnicas de diagnóstico como Tomografia por emissão de Fóton Único (Single photon Emission Computed Tomography - SPECT), cintilografia, e Ressonância Magnética Nuclear (RMN). Neste contexto, sua aplicação em diagnóstico de sistema linfático e linfonodo sentinela recebe atenção especial. O emprego de técnicas de diagnóstico pode ser considerado uma ferramenta importante para a exploração de sistemas no organismo humano assim como para a investigação de caminhos moleculares envolvidos nos processos de diversas doenças. O uso de metodologias de modelagem molecular e estratégias de desenvolvimento de fármacos assistidas computacionalmente também pode fornecer informações valiosas para o planejamento e o desenvolvimento racional de novos radiofármacos

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Nanomedicine: Perspective and promises with ligand-directed molecular imaging

Cited by 95 publications

References 192 publications

Quantitative ¹H MRI, ¹⁹F MRI, and ¹⁹F MRS of cell‐internalized perfluorocarbon paramagnetic nanoparticles

Quantitative ¹H MRI, ¹⁹F MRI, and ¹⁹F MRS of cell‐internalized perfluorocarbon paramagnetic nanoparticles

Impact of nanotechnology in breast cancer

Polymeric micelles and molecular modeling applied to the development of radiopharmaceuticals

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Nanomedicine: Perspective and promises with ligand-directed molecular imaging

Cited by 95 publications

References 192 publications

Quantitative 1H MRI, 19F MRI, and 19F MRS of cell‐internalized perfluorocarbon paramagnetic nanoparticles

Quantitative 1H MRI, 19F MRI, and 19F MRS of cell‐internalized perfluorocarbon paramagnetic nanoparticles

Impact of nanotechnology in breast cancer

Polymeric micelles and molecular modeling applied to the development of radiopharmaceuticals

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Product

Resources

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Quantitative ¹H MRI, ¹⁹F MRI, and ¹⁹F MRS of cell‐internalized perfluorocarbon paramagnetic nanoparticles

Quantitative ¹H MRI, ¹⁹F MRI, and ¹⁹F MRS of cell‐internalized perfluorocarbon paramagnetic nanoparticles