Gadolinium-conjugated TiO2-DNA oligonucleotide nanoconjugates show prolonged intracellular retention period and T1-weighted contrast enhancement in magnetic resonance images

Paunesku, Tatjana; Ke, Tianyi; Dharmakumar, Rohan; Mascheri, Nicole; Wu, Aiguo; Lai, Barry; Vogt, Stefan; Mäser, J.; Thurn, Kenneth T.; Szolc-Kowalska, Barbara; Larson, Andrew C.; Bergan, Raymond C.; Omary, Reed A.; Li, Debiao; Lü, Zheng Rong; Woloschak, Gayle E.

doi:10.1016/j.nano.2008.04.004

Cited by 44 publications

(43 citation statements)

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“…The scale in b also applies to a. (20,21). To our knowledge, our study represents the first functional characterization of murine DCIS with DCE MR imaging, which has an advantage over characterization of DCIS in humans: Ducts with DCIS can be clearly depicted without contrast material injection; therefore, an ROI can be placed directly on the neoplastic duct to enable one to more accurately measure its kinetic parameters, thereby minimizing the partial voluming that complicates human kinetic data.…”

Section: Discussionmentioning

confidence: 99%

Ductal Carcinoma in Situ: X-ray Fluorescence Microscopy and Dynamic Contrast-enhanced MR Imaging Reveals Gadolinium Uptake within Neoplastic Mammary Ducts in a Murine Model

Jansen¹,

Paunesku²,

Fan³

et al. 2009

Radiology

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Purpose:To combine dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging with x-ray fluorescence microscopy (XFM) of mammary gland tissue samples from mice to identify the spatial distribution of gadolinium after intravenous injection. Materials and Methods:C3(1) Sv-40 large T antigen transgenic mice (n ϭ 23) were studied with institutional animal care and use committee approval. Twelve mice underwent DCE MR imaging after injection of gadodiamide, and gadolinium concentrationtime curves were fit to a two-compartment pharmacokinetic model with the following parameters: transfer constant (K trans ) and volume of extravascular extracellular space per unit volume of tissue (v e ). Eleven mice received gadodiamide before XFM. These mice were sacrificed 2 minutes after injection, and frozen slices containing ducts distended with murine ductal carcinoma in situ (DCIS) were prepared for XFM. One mouse received saline and served as the control animal. Elemental gadolinium concentrations were measured in and around the ducts with DCIS. Hematoxylin-eosin-stained slices of mammary tissues were obtained after DCE MR imaging and XFM. Results:Ducts containing DCIS were unambiguously identified on MR images. DCE MR imaging revealed gadolinium uptake along the length of ducts with DCIS, with an average K trans of 0.21 min Ϫ1 Ϯ 0.14 (standard deviation) and an average v e of 0.40 Ϯ 0.16. XFM revealed gadolinium uptake inside ducts with DCIS, with an average concentration of 0.475 mmol/L Ϯ 0.380; the corresponding value for DCE MR imaging was 0.30 mmol/L Ϯ 0.13. Conclusion:These results provide insight into the physiologic basis of contrast enhancement of DCIS lesions on DCE MR images: Gadolinium penetrates and collects inside neoplastic ducts. RSNA, 2009 Note: This copy is for your personal, non-commercial use only. To order presentation-ready copies for distribution to your colleagues or clients, use the Radiology Reprints form at the end of this article.T he sensitivity and specificity of dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging in the early detection of invasive cancers have been shown to be equal or superior to those of x-ray mammography (1). However, this has not been consistently demonstrated for ductal carcinoma in situ (DCIS), which is a nonobligate precursor to invasive breast cancer, in which cancer cells are still confined by the basement membrane of mammary ducts. Because DCIS is the earliest stage of breast cancer and has the best prognosis, it is likely that further improvements in the detection of breast cancers at a preinvasive stage may improve patient outcomes. Some reports have shown decreased diagnostic accuracy of DCE MR imaging for DCIS (2,3), while others have shown comparable or even higher performance compared with that of x-ray mammography (4,5). The sensitivity of DCE MR imaging for detection of DCIS may be compromised if the lesion does not exhibit sufficient gadolinium uptake or if it is obscured by strongly enhancing parenchyma (6,7). Even when D...

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Section: Discussionmentioning

confidence: 99%

Ductal Carcinoma in Situ: X-ray Fluorescence Microscopy and Dynamic Contrast-enhanced MR Imaging Reveals Gadolinium Uptake within Neoplastic Mammary Ducts in a Murine Model

Jansen¹,

Paunesku²,

Fan³

et al. 2009

Radiology

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“…In effect, these results clearly show that, YO NCs possesses both fluorescence and magnetic functionalities suitable for bi-modal imaging. Nanocrystals based MR imaging has significant advantages over currently used Gd 3þ -DTPA complexes because of possible disease targeting capability and adjustable (PEGylation) in vivo circulation life time [54][55][56][57]. In addition, when each individual NCs, with high local concentration of magnetic ions, are accumulated within intra-cellular region, better contrast of tissue will be possible.…”

Section: Magnetic Resonance Imaging Using Yo Ncsmentioning

confidence: 99%

Folate receptor targeted, rare-earth oxide nanocrystals for bi-modal fluorescence and magnetic imaging of cancer cells

et al. 2010

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“…SR-XRF imaging confirmed that they were specifically retained in the mitochondria or nucleoli, thus creating a locally increased concentration of the oligonucleotide. In other studies, nanoconjugates composed of TiO 2 nanoparticles with DNA oligonucleotides and a gadolinium contrast agent were synthesized for use in magnetic resonance imaging (Endres et al 2008;Paunesku et al 2008). Transfection of cultured cancer cells with these nanoconjugates showed them to be superior to the free contrast agent of the same formulation with regard to intracellular accumulation, retention and subcellular localization.…”

Section: Examples Of Applicationmentioning

confidence: 99%

Bio-metals imaging and speciation in cells using proton and synchrotron radiation X-ray microspectroscopy

Ortega

Devès

Carmona

2009

J. R. Soc. Interface.

139

131

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The direct detection of biologically relevant metals in single cells and of their speciation is a challenging task that requires sophisticated analytical developments. The aim of this article is to present the recent achievements in the field of cellular chemical element imaging, and direct speciation analysis, using proton and synchrotron radiation X-ray micro-and nanoanalysis. The recent improvements in focusing optics for MeV-accelerated particles and keV X-rays allow application to chemical element analysis in subcellular compartments. The imaging and quantification of trace elements in single cells can be obtained using particle-induced X-ray emission (PIXE). The combination of PIXE with backscattering spectrometry and scanning transmission ion microscopy provides a high accuracy in elemental quantification of cellular organelles. On the other hand, synchrotron radiation X-ray fluorescence provides chemical element imaging with less than 100 nm spatial resolution. Moreover, synchrotron radiation offers the unique capability of spatially resolved chemical speciation using micro-X-ray absorption spectroscopy. The potential of these methods in biomedical investigations will be illustrated with examples of application in the fields of cellular toxicology, and pharmacology, bio-metals and metal-based nano-particles.

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Gadolinium-conjugated TiO2-DNA oligonucleotide nanoconjugates show prolonged intracellular retention period and T1-weighted contrast enhancement in magnetic resonance images

Cited by 44 publications

References 24 publications

Ductal Carcinoma in Situ: X-ray Fluorescence Microscopy and Dynamic Contrast-enhanced MR Imaging Reveals Gadolinium Uptake within Neoplastic Mammary Ducts in a Murine Model

Ductal Carcinoma in Situ: X-ray Fluorescence Microscopy and Dynamic Contrast-enhanced MR Imaging Reveals Gadolinium Uptake within Neoplastic Mammary Ducts in a Murine Model

Folate receptor targeted, rare-earth oxide nanocrystals for bi-modal fluorescence and magnetic imaging of cancer cells

Bio-metals imaging and speciation in cells using proton and synchrotron radiation X-ray microspectroscopy

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