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MR Nanosized Contrast Agents Used to Visualize, Quantify Tumor Angiogenesis

By MedImaging International staff writers
Posted on 24 Aug 2010
Scientists have incorporated nanotechnology, material science, and the clinical imaging modality magnetic resonance imaging (MRI) to create a nanosized probe capable of noninvasively visualizing and quantifying the blood vessel growth in tumors in a preclinical model.

Angiogenesis is vital for sustained tumor growth and cancer metastasis. Clinically available therapies to suppress the growth of these vessels have been available to improve patient survival in some cancer types. Accurate detection and quantification of blood vessel growth using nonsurgical methods would greatly complement current therapies and allow physicians to quickly assess treatment regimens and adjust them as necessary.

In new research published in the August 2010 issue of the journal Experimental Biology and Medicine, scientists have incorporated nanotechnology, material science, and the clinical imaging modality MRI, to create a nanosized probe capable of noninvasively visualizing and quantifying the blood vessel growth in tumors in a preclinical model. The study was conducted by Chase Kessinger, as part of his Ph.D. thesis in cancer molecular imaging, working with Dr. Jinming Gao and other colleagues, at the University of Texas (UT) Southwestern Medical Center at Dallas (USA).

Dr. Gao stated, "Imaging tumor angiogenesis is important in early detection, tumor stratification, and post-therapy assessment of antiangiogenic drugs. Current clinical modality for angiogenesis imaging utilizes dynamic contrast enhancement MRI by small molecular contrast agents. The method is based on the measurement of permeability of the contrast probes in well-established solid tumors and is not very specific to detect the early on-set of vessel formation. The dual functional nanoprobes aim to image angiogenesis-specific tumor markers that are overly expressed in the tumor vasculature during the early phase of angiogenesis.”

Together, the research team relied on nanotechnology and established superparamagnetic micellar nanoprobes (50 nm -70 nm in diameter) with greatly improved MRI sensitivity over conventional small molecular agents. The nanoprobe surface was functionalized with a cyclic peptide that can specifically bind to αvβ3 integrins that are overexpressed on the tumor endothelial cells. The nanoprobes also had a fluorescent moiety employed for the validation of targeted delivery to the tumor endothelial cells. Studies in cancer cells confirmed the increased uptake of nanoprobes compared to nontargeted-nanoparticles. In collaboration with Dr. Masaya Takahashi and coworkers in the Advanced Imaging Research Center at UT Southwestern Medical Center, the research team utilized a three-dimensional (3D) high-resolution acquisition method to visualize the accumulation of the micelle nanoprobes in tumors.

"Conventional image analysis of angiogenesis relies on the evaluation of ‘hot spot' densities in 2D images. The 3D high resolution method allowed for the connection of the isolated hot spots in 2D slices into 3D network structures, which greatly improves the accuracy of vessel identification and quantification,” noted Dr. Gao.

In preclinical animal tumor models, MR imaging of the targeted contrast probes yielded vascularized network structures in 3D tumor images. The enhanced visualization allowed for a more accurate quantification of tumor angiogenesis. The study's findings demonstrated a considerable increase of contrast specificity of angiogenic vessels by the targeted nanoprobes over nontargeted micelles. These targeted nanoprobes may provide a useful contrast probe design for the clinical diagnosis of tumor angiogenesis.

Steven R. Goodman, editor-in-chief of Experimental Biology and Medicine, commented, "Kessinger et al working at the interface of nanotechnology, material science, and the clinical imaging modality MRI have created a nanosized probe capable of noninvasively visualizing and quantifying the blood vessel growth in tumors in a preclinical model. This should be an important tool for clinical observation of tumor angiogenesis.”

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University of Texas Southwestern Medical Center at Dallas


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89 (44.107437133789): SELECT id,name,title FROM jos_deeppockets WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id != 294743300 AND id != 294743301 AND id != 294743302 AND id != 294743303 AND id != 294743304 AND id != 294743305 AND id != 294743306 AND id != 294743307 AND id != 294743308 AND id != 294743309 AND id != 294743310 AND metakey != 'aacc' ORDER BY `ordering`
90 (46.014785766602): SELECT show_live FROM jos_com_show_setting LIMIT 1
91 (29.802322387695): SELECT show_live FROM jos_com_show_setting LIMIT 1
92 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
93 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1
94 (35.04753112793): SELECT show_live FROM jos_com_show_setting LIMIT 1
95 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1
96 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
97 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
98 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1
99 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1
100 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1
101 (27.179718017578): SELECT show_live FROM jos_com_show_setting LIMIT 1
102 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1
103 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
104 (62.942504882812): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294730829 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294730829 AND published='1' LIMIT 1
105 (43.869018554688): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294730829 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294730829 AND published='1' LIMIT 1
106 (46.014785766602): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294730829 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
107 (47.206878662109): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294730829 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
108 (73.909759521484): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294730829 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294730829 AND published='1' LIMIT 1
109 (43.153762817383): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294730829 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294730829 AND published='1' LIMIT 1
110 (67.949295043945): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294730829 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
111 (393.86749267578): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294730829 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
112 (530.95817565918): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1
113 (298.97689819336): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1
114 (76.770782470703): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294730829 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294730829 AND published='1' LIMIT 1
115 (46.014785766602): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294730829 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294730829 AND published='1' LIMIT 1
116 (46.014785766602): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294730829 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294730829 AND published='1' LIMIT 1
117 (37.908554077148): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294730829 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294730829 AND published='1' LIMIT 1
118 (41.007995605469): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294730829 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294730829 AND published='1' LIMIT 1
119 (68.187713623047): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294730829 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294730829 AND published='1' LIMIT 1
120 (46.968460083008): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294730829 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294730829 AND published='1' LIMIT 1
121 (36.001205444336): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294730829 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294730829 AND published='1' LIMIT 1
122 (195.98007202148): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`
123 (!!!!! 18697.97706604): SELECT * FROM jos_deeppockets WHERE jos_deeppockets.cat = 10 AND jos_deeppockets.type = 'deeppockets_item' AND jos_deeppockets.published = 1 AND jos_deeppockets.created + INTERVAL 14 DAY >= NOW() ORDER BY jos_deeppockets.hits DESC LIMIT 7
124 (405.07316589355): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294730829 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294730829 AND type='deeppockets_item' AND published='1' LIMIT 1
125 (!!!!! 7209.0625762939): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3
126 (122.0703125): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3
127 (47.922134399414): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1
128 (30.994415283203): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1
129 (58.889389038086): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1
130 (31.948089599609): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1
131 (202.17895507812): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1
132 (34.093856811523): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1
133 (30.994415283203): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1
134 (27.894973754883): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1
135 (387.90702819824): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294730829 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
136 (241.04118347168): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294730829 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
137 (119.92454528809): SELECT name FROM jos_deeppockets WHERE id=212
138 (30.040740966797): SELECT name FROM jos_deeppockets WHERE id=212
139 (514.03045654297): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))212((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
140 (421.04721069336): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))212((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
141 (113.96408081055): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294730829 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294730829 AND published='1' LIMIT 1
142 (46.014785766602): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294730829 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294730829 AND published='1' LIMIT 1
143 (!!!!! 5023.0026245117): TRUNCATE TABLE jos_trademed_module
144 (471.11511230469): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294730829 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
145 (68.902969360352): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294730829 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
146 (386.95335388184): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294730829 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
147 (65.088272094727): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294730829 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
148 (56.982040405273): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294730829 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294730829 AND published='1' LIMIT 1
149 (56.982040405273): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294730829 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294730829 AND published='1' LIMIT 1
150 (!!!!! 1035.9287261963): SELECT jos_item.* FROM jos_item INNER JOIN jos_number ON jos_item.numberID=jos_number.id WHERE 1=1 AND (jos_item.imgMini<>'') AND jos_item.type='L' AND jos_item.numberID= ( SELECT jos_number.id FROM jos_number WHERE jos_number.journalID IN (10) and jos_number.id in (select distinct jos_number.id from jos_number join jos_item on jos_item.numberid=jos_number.id where jos_item.type='P') ORDER BY (CONVERT(SUBSTRING(issue,1,2),SIGNED) + (CONVERT(SUBSTRING(issue,3,2),SIGNED)*100)) DESC LIMIT 0,1 ) ORDER BY RAND() DESC LIMIT 6
151 (56.028366088867): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294730829 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294730829 AND published='1' LIMIT 1
152 (40.054321289062): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294730829 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294730829 AND published='1' LIMIT 1
153 (32.901763916016): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294730829 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294730829 AND type='deeppockets_item' AND published='1' LIMIT 1
154 (27.894973754883): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=212 or channel_id is null)
155 (25.98762512207): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=212 or channel_id is null)
156 (26.941299438477): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1
157 (292.06275939941): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294730829 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294730829 AND published='1' LIMIT 1
158 (93.936920166016): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294730829 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294730829 AND published='1' LIMIT 1
159 (150.91896057129): select jos_twitters.link from jos_twitters where cat=10
160 (102.99682617188): select jos_facebook.link from jos_facebook where cat=10
161 (185.01281738281): select jos_google_plus.link from jos_google_plus where cat=10
162 (92.983245849609): select jos_linkedin.link from jos_linkedin where cat=10
163 (589.13230895996): update jos_bannersmanager_banner set impmade=impmade+1 where id in(14615,14202,14203)
164 (!!!!! 1031.8756103516): insert into jos_banners_delta values (14615,'2025-06-28 02:24:11','216.73.216.249','view'),(14202,'2025-06-28 02:24:11','216.73.216.249','view'),(14203,'2025-06-28 02:24:11','216.73.216.249','view')