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MRI Technology Enables Noninvasive Monitoring of Emergent Cell Therapies

By MedImaging International staff writers
Posted on 07 Oct 2014
Cellular therapeutics, the application of using intact cells to treat and cure disease, is an important potential new therapeutic application, but it is hampered by the inability of clinicians and scientists to effectively monitor the destination, movements, and perseverance of these cells in patients without having to use invasive procedures, such as tissue sampling.

In a study published September 19, 2014, in the online journal Magnetic Resonance in Medicine, researchers from the University of California (UC), San Diego School of Medicine (USA), University of Pittsburgh, and elsewhere describe the first human tests of using a perfluorocarbon (PFC) tracer in combination with noninvasive magnetic resonance imaging (MRI) scanning to track therapeutic immune cells injected into colorectal cancer patients.

“Initially, we see this technique used for clinical trials that involve tests of new cell therapies,” said first author Eric T. Ahrens, PhD, professor in the department of radiology at UC San Diego. “Clinical development of cell therapies can be accelerated by providing feedback regarding cell motility, optimal delivery routes, individual therapeutic doses, and engraftment success.”

Currently, there is no accepted way to image cells in the human body that includes a broad range of cell types and diseases. Earlier strategies have employed metal ion-based vascular MRI contrast agents and radioisotopes. The former have been shown to be difficult to differentiate in vivo; the latter raise apprehensions about radiation toxicity and do not provide the anatomic facets available with MRI scans. “This is the first human PFC cell tracking agent, which is a new way to do MRI cell tracking,” said Dr. Ahrens. “It’s the first example of a clinical MRI agent designed specifically for cell tracking.”

Researchers utilized a PFC tracer agent and an MRI technique that directly identifies fluorine atoms in labeled cells. Fluorine atoms naturally occur in extremely low concentrations in the body, making it easier to see cells labeled with fluorine using MRI scanning. In this instance, the engineered and labeled dendritic cells—powerful stimulators of the immune system—were first prepared from white blood cells extracted from the patient. The cells were then injected into patients with stage 4 metastatic colorectal cancer to trigger an anticancer T-cell immune response.

The published study did not evaluate the effectiveness of the cell therapy, but instead the ability of researchers to detect the labeled cells and monitor what occurred to them. Ahrens said the technique worked as expected, with the unanticipated finding that only half of the delivered cell vaccine remained at the inoculation site after 24 hours.

“The imaging agent technology has been to shown to be able to tag any cell type that is of interest,” Dr. Ahrens concluded. “It is a platform imaging technology for a wide range of diseases and applications, which might also speed development of relevant therapies. Noninvasive cell tracking may help lower regulatory barriers. For example, new stem cell therapies can be slow to obtain regulatory approvals in part because it is difficult, if not impossible, with current approaches to verify survival and location of transplanted cells. And cell therapy trials generally have a high cost per patient. Tools that allow the investigator to gain a ‘richer’ data set from individual patients mean it may be possible to reduce patient numbers enrolled in a trial, thus reducing total trial cost.”

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91 (!!!!! 4947.9007720947): 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`
92 (72.002410888672): SELECT show_live FROM jos_com_show_setting LIMIT 1
93 (35.04753112793): SELECT show_live FROM jos_com_show_setting LIMIT 1
94 (29.087066650391): SELECT show_live FROM jos_com_show_setting LIMIT 1
95 (295.87745666504): SELECT show_live FROM jos_com_show_setting LIMIT 1
96 (215.05355834961): SELECT show_live FROM jos_com_show_setting LIMIT 1
97 (31.948089599609): SELECT show_live FROM jos_com_show_setting LIMIT 1
98 (181.19812011719): SELECT show_live FROM jos_com_show_setting LIMIT 1
99 (329.01763916016): SELECT show_live FROM jos_com_show_setting LIMIT 1
100 (231.02760314941): SELECT show_live FROM jos_com_show_setting LIMIT 1
101 (!!!!! 1583.8146209717): SELECT show_live FROM jos_com_show_setting LIMIT 1
102 (56.982040405273): SELECT show_live FROM jos_com_show_setting LIMIT 1
103 (!!!!! 4333.9729309082): SELECT show_live FROM jos_com_show_setting LIMIT 1
104 (557.89947509766): SELECT show_live FROM jos_com_show_setting LIMIT 1
105 (47.922134399414): SELECT show_live FROM jos_com_show_setting LIMIT 1
106 (128.98445129395): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294755035 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294755035 AND published='1' LIMIT 1
107 (771.04568481445): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294755035 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294755035 AND published='1' LIMIT 1
108 (!!!!! 2681.0169219971): 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=294755035 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
109 (!!!!! 2792.1199798584): 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=294755035 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
110 (!!!!! 4078.8650512695): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294755035 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294755035 AND published='1' LIMIT 1
111 (370.97930908203): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294755035 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294755035 AND published='1' LIMIT 1
112 (!!!!! 1522.0642089844): 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=294755035 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
113 (!!!!! 7411.003112793): 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=294755035 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
114 (648.97537231445): 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=294755033 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
115 (566.00570678711): 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=294755033 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
116 (!!!!! 6360.0540161133): 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
117 (854.0153503418): 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
118 (!!!!! 2645.9693908691): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294755035 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294755035 AND published='1' LIMIT 1
119 (!!!!! 4803.8959503174): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294755035 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294755035 AND published='1' LIMIT 1
120 (!!!!! 2750.8735656738): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294755035 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294755035 AND published='1' LIMIT 1
121 (634.90867614746): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294755035 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294755035 AND published='1' LIMIT 1
122 (517.84515380859): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294755035 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294755035 AND published='1' LIMIT 1
123 (746.01173400879): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294755035 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294755035 AND published='1' LIMIT 1
124 (108.00361633301): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294755035 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294755035 AND published='1' LIMIT 1
125 (190.97328186035): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294755035 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294755035 AND published='1' LIMIT 1
126 (!!!!! 1060.962677002): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`
127 (!!!!! 83403.825759888): 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
128 (753.87954711914): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294755035 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294755035 AND type='deeppockets_item' AND published='1' LIMIT 1
129 (100.85105895996): ( 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
130 (60.796737670898): ( 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
131 (111.10305786133): 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
132 (53.882598876953): 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
133 (77.009201049805): 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
134 (49.114227294922): 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
135 (46.968460083008): 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
136 (42.915344238281): 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
137 (58.889389038086): 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
138 (44.107437133789): 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
139 (!!!!! 1040.9355163574): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294755035 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
140 (760.07843017578): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294755035 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
141 (295.16220092773): SELECT name FROM jos_deeppockets WHERE id=212
142 (220.06034851074): SELECT name FROM jos_deeppockets WHERE id=212
143 (926.97143554688): 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((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
144 (!!!!! 1042.1276092529): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))212((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
145 (406.98051452637): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294755035 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294755035 AND published='1' LIMIT 1
146 (262.02201843262): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294755035 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294755035 AND published='1' LIMIT 1
147 (!!!!! 25654.077529907): TRUNCATE TABLE jos_trademed_module
148 (286.10229492188): 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=294755035 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
149 (177.86026000977): 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=294755035 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
150 (602.96058654785): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294755035 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
151 (103.95050048828): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294755035 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
152 (801.08642578125): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294755035 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294755035 AND published='1' LIMIT 1
153 (!!!!! 1949.0718841553): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294755035 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294755035 AND published='1' LIMIT 1
154 (!!!!! 1556.8733215332): 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
155 (124.93133544922): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294755035 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294755035 AND published='1' LIMIT 1
156 (81.062316894531): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294755035 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294755035 AND published='1' LIMIT 1
157 (246.04797363281): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294755035 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294755035 AND type='deeppockets_item' AND published='1' LIMIT 1
158 (118.01719665527): 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=0 or channel_id is null)
159 (144.95849609375): 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=0 or channel_id is null)
160 (101.08947753906): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1
161 (!!!!! 2954.0061950684): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294755035 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294755035 AND published='1' LIMIT 1
162 (112.05673217773): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294755035 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294755035 AND published='1' LIMIT 1
163 (485.89706420898): select jos_twitters.link from jos_twitters where cat=10
164 (42.915344238281): select jos_facebook.link from jos_facebook where cat=10
165 (38.14697265625): select jos_google_plus.link from jos_google_plus where cat=10
166 (87.976455688477): select jos_linkedin.link from jos_linkedin where cat=10