Molecular Optical Imaging of Therapeutic Targets of Cancer

Sokolov, Konstantin; Nida, Dawn; Descour, Michael R.; Lacy, Alicia; Levy, Matthew; Hall, Brad; Dharmawardhane, Su; Ellington, Andrew D.; Korgel, Brian A.; Richards‐Kortum, Rebecca

doi:10.1016/s0065-230x(06)96011-4

Cited by 27 publications

(12 citation statements)

References 130 publications

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“…Tumor tissues changes at the molecular level occur prior to any detectable tumor size changes, thus the ability to dynamically and quantitatively assess and track the molecular profile in vivo could provide substantial patient benefit. Additionally there is good evidence to support the fact that signaling pathways change in response to receptor blocking therapy 10, and so having the ability to track dynamic changes could significantly improve the potential of developing multi-receptor targeting approaches.…”

Section: Introductionmentioning

confidence: 99%

Detecting Epidermal Growth Factor Receptor Tumor Activity In Vivo During Cetuximab Therapy of Murine Gliomas

et al. 2010

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Rationale and Objectives Noninvasive molecular imaging of glioma tumor receptor activity was assessed with diagnostic in vivo fluorescence monitoring during targeted therapy. The study goals were to assess the range of use for treatment monitoring and stratification of tumor types using EGFR status with administration of fluorescently labeled epidermal growth factor (EGF), and determine its utility for tumor detection compared to magnetic resonance imaging (MRI). Materials and Methods Epidermal growth factor receptor positive and negative (EGFR+ and EGFR−) glioma tumor lines (U251-GFP and 9L-GFP, respectively) were used to assess these goals, having a 20-fold difference between their EGF uptakes. Results Treatment with cetuximab, in the EGFR+ tumor-bearing animals led to decreased EGF tumor uptake, whereas for the EGFR− tumors no change in fluorescence signal followed treatment. This diagnostic difference in EGFR expression could be used to stratify the tumor-bearing animals into groups of potential responders and non-responders, and receiver operator characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.92 in separating these tumors. The non-localized growth pattern of U251-GFP tumors resulted in detection difficulty via standard MRI, however high EGFR expression made them detectable through fluorescence imaging (ROC-AUC = 1.0). The EGFR+, U251-GFP tumor-bearing animals could be noninvasively stratified into treated and untreated groups based on fluorescence intensity difference (p = 0.035, ROC-AUC = 0.90). Conclusions EGFR expression was tracked in vivo with fluorescence, and determined to be of use for stratification of EGFR+ and EGFR− tumors, detection of EGFR+ tumors and monitoring of molecular therapy.

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Section: Introductionmentioning

confidence: 99%

Detecting Epidermal Growth Factor Receptor Tumor Activity In Vivo During Cetuximab Therapy of Murine Gliomas

et al. 2010

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“…Optical techniques that exploit exogenous contrast agents, such as antibody-conjugated gold nanoparticles 11,12 or fluorescence molecules, 13,14 are currently being investigated to enhance a surgeon's ability to identify malignancy, with one possible use being intraoperative margin assessment. A contrast agent such as 5-aminolevulinic acid ͑ALA͒ is one potential candidate for margin assessment.…”

Section: Introductionmentioning

confidence: 99%

Preferential accumulation of 5-aminolevulinic acid-induced protoporphyrin IX in breast cancer: a comprehensive study on six breast cell lines with varying phenotypes

et al. 2010

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Abstract. We describe the potential of 5-aminolevulinic acid ͑ALA͒-induced protoporphyrin IX ͑PpIX͒ fluorescence as a source of contrast for margin detection in commonly diagnosed breast cancer subtypes. Fluorescence intensity of PpIX in untreated and ALA-treated normal mammary epithelial and breast cancer cell lines of varying estrogen receptor expression were quantitatively imaged with confocal microscopy. Percentage change in fluorescence intensity integrated over 610-700 nm ͑attributed to PpIX͒ of posttreated compared to pretreated cells showed statistically significant differences between four breast cancer and two normal mammary epithelial cell lines. However, a direct comparison of post-treatment PpIX fluorescence intensities showed no differences between breast cancer and normal mammary epithelial cell lines due to confounding effects by endogenous fluorescence from flavin adenine dinucleotide ͑FAD͒. Clinically, it is impractical to obtain pre-and post-treatment images. Thus, spectral imaging was demonstrated as a means to remove the effects of endogenous FAD fluorescence allowing for discrimination between posttreatment PpIX fluorescence of four breast cancer and two normal mammary epithelial cell lines. Fluorescence spectral imaging of ALAtreated breast cancer cells showed preferential PpIX accumulation regardless of malignant phenotype and suggests a useful contrast mechanism for discrimination of residual cancer at the surface of breast tumor margins.

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“…Their size is similar to biological macromolecules [3,4] and their surfaces provide a bioconjugation scaffold to tether biocompatible coatings [2,5,6] and biologically-relevant recognition molecules like nucleic acids [6,7], peptide fragments [4], and antibodies [2,3,8]. Nanoparticles can be used to map cellular components and monitor and track them in real time [5,9] and can also be used as drug delivery vehicles [10,11] and therapeutic agents [12-14]. For example, superparamagnetic iron oxide nanoparticles are commercially available as magnetic resonance imaging (MRI) contrast agents [15,16]; although higher contrast is still desired and new magnetic nanoparticles are being studied and developed for these purposes [17-21].…”

Section: Introductionmentioning

confidence: 99%

Multifunctional particles: Magnetic nanocrystals and gold nanorods coated with fluorescent dye-doped silica shells

Heitsch

Smith

Patel

et al. 2008

Journal of Solid State Chemistry

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Multifunctional colloidal core-shell nanoparticles of magnetic nanocrystals (of iron oxide or FePt) or gold nanorods encapsulated in silica shells doped with the fluorescent dye, Tris(2,2′-bipyridyl) dichlororuthenium(II) hexahydrate (Rubpy) were synthesized. The as-prepared magnetic nanocrystals are initially hydrophobic and were coated with silica using a microemulsion approach, while the as-prepared gold nanorods are hydrophilic and were coated with silica using a Stöber-type of process. Each approach yielded monodisperse nanoparticles with uniform fluorescent dye-doped silica shells. These colloidal heterostructures have the potential to be used as dual-purpose tagsexhibiting a fluorescent signal that could be combined with either dark-field optical contrast (in the case of the gold nanorods), or enhanced contrast in magnetic resonance images (in the case of magnetic nanocrystal cores). The optical and magnetic properties of the fluorescent silica-coated gold nanorods and magnetic nanocrystals are reported.

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Molecular Optical Imaging of Therapeutic Targets of Cancer

Cited by 27 publications

References 130 publications

Detecting Epidermal Growth Factor Receptor Tumor Activity In Vivo During Cetuximab Therapy of Murine Gliomas

Detecting Epidermal Growth Factor Receptor Tumor Activity In Vivo During Cetuximab Therapy of Murine Gliomas

Preferential accumulation of 5-aminolevulinic acid-induced protoporphyrin IX in breast cancer: a comprehensive study on six breast cell lines with varying phenotypes

Multifunctional particles: Magnetic nanocrystals and gold nanorods coated with fluorescent dye-doped silica shells

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