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PET Probes Provide Clues into Immune Cellular Function

By MedImaging International staff writers
Posted on 17 Jun 2010
A commonly used probe for positron emission tomography (PET) scanning and a new probe developed by researchers reveal different functions in diverse cells of the immune system, providing a noninvasive and much clearer outlook of an immune response in action.

The probes, commonly used fluorodeoxyglucose (FDG) that measures cellular glucose metabolism, and FAC (fluoroarabinofuranosyl cytosine), developed at the University of California, Los Angeles (UCLA; USA), and which measures the activity of a distinct biochemical pathway, work better when used in combination than either does alone. In addition to revealing the extent and cellular composition of an immune response, the probes also may be useful in evaluating therapies that target different cellular components of the immune system, according to Dr. Owen Witte, a UCLA professor of microbiology, immunology, and molecular genetics, and senior author of the study.

"We demonstrated with this study that each probe targets different cells in the immune system with a high degree of specificity,” said Dr. Witte, director of the UCLA Broad Stem Cell Research Center. "When cells are activated to do their job as an immune cell, the FDG probe is good at recognizing the subset of activated macrophages, while the FAC probe is good at recognizing the activated lymphocytes, as well as the macrophages. When tested sequentially, the combined information from the scans using the two probes gives you a better status of immune response.”

The study, with lead author Evan Nair-Gill, a student in the campus' Medical Scientist Training Program, was conducted on mice bearing virally induced sarcomas. The article was published May 18, 2010, in the early online edition of the Journal of Clinical Investigation. Testing the probes in humans is the next step.

The scans provide insights into how the immune system works, for example, in response to cancer or autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis, according to Dr. Witte. They also could be used to see how therapies, such as vaccines and monoclonal antibodies meant to stimulate an immune response, are functioning within the body of a patient. "This could give us another way to measure the efficacy of certain drugs,” Dr. Witte said. "With some drugs, you could measure a change in the immune response within a week.”

If the drugs are working, physicians could stay the course. If they are not working or not working well enough, the therapy could be discontinued, sparing the patient a months-long exposure to an ineffective drug. The next step will be evaluating the two probes in humans with a range of diseases, including cancer and autoimmune disorders, to confirm the work.

Dr. Witte and his colleagues licensed the FAC probe to Sofie Biosciences (Culver City, CA, USA; www.sofie-biosciences.com), which is owned in part by Dr. Witte and other UCLA faculty members. Researchers created the small molecule by slightly altering the molecular structure of one of the most commonly used chemotherapy drugs, gemcitabine. They then added a radiolabel so the cells that take in the probe can be seen during PET scanning.

The probe measures the activity of an essential cell biochemical pathway called the DNA salvage pathway, which acts as a recycling mechanism that helps with DNA replication and repair. All cells use this biochemical pathway to different levels. However, in lymphocytes and macrophages that are proliferating during an immune response, the pathway is activated to very high levels. Because of that, the probe accumulates at high levels in those cells, reported Dr. Witte.

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95 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1
96 (35.04753112793): SELECT show_live FROM jos_com_show_setting LIMIT 1
97 (28.848648071289): SELECT show_live FROM jos_com_show_setting LIMIT 1
98 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
99 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
100 (27.179718017578): SELECT show_live FROM jos_com_show_setting LIMIT 1
101 (28.133392333984): 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 (64.13459777832): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729817 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729817 AND published='1' LIMIT 1
105 (42.915344238281): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729817 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729817 AND published='1' LIMIT 1
106 (51.021575927734): 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=294729817 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
107 (49.114227294922): 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=294729817 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
108 (76.055526733398): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729817 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729817 AND published='1' LIMIT 1
109 (44.822692871094): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729817 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729817 AND published='1' LIMIT 1
110 (51.975250244141): 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=294729817 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
111 (600.09956359863): 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=294729817 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
112 (646.11434936523): 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 (378.13186645508): 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 (77.962875366211): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729817 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729817 AND published='1' LIMIT 1
115 (46.014785766602): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729817 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729817 AND published='1' LIMIT 1
116 (47.922134399414): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729817 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729817 AND published='1' LIMIT 1
117 (36.954879760742): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729817 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729817 AND published='1' LIMIT 1
118 (43.153762817383): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729817 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729817 AND published='1' LIMIT 1
119 (94.175338745117): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729817 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729817 AND published='1' LIMIT 1
120 (41.961669921875): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729817 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729817 AND published='1' LIMIT 1
121 (37.908554077148): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729817 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729817 AND published='1' LIMIT 1
122 (273.9429473877): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`
123 (!!!!! 21103.858947754): 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 (607.01370239258): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294729817 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294729817 AND type='deeppockets_item' AND published='1' LIMIT 1
125 (!!!!! 8655.0712585449): ( 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 (98.943710327148): ( 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 (133.99124145508): 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 (58.174133300781): 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 (92.029571533203): 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 (30.994415283203): 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 (329.97131347656): 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 (36.001205444336): 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 (32.901763916016): 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 (34.093856811523): 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 (475.88348388672): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729817 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
136 (518.798828125): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729817 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
137 (82.969665527344): SELECT name FROM jos_deeppockets WHERE id=213
138 (59.127807617188): SELECT name FROM jos_deeppockets WHERE id=213
139 (599.86114501953): 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 '((;)|(^))213((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
140 (431.06079101562): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))213((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
141 (67.949295043945): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729817 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729817 AND published='1' LIMIT 1
142 (51.021575927734): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729817 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729817 AND published='1' LIMIT 1
143 (!!!!! 9465.217590332): TRUNCATE TABLE jos_trademed_module
144 (138.99803161621): 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=294729817 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
145 (91.075897216797): 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=294729817 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
146 (941.99180603027): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729817 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
147 (72.002410888672): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729817 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
148 (85.115432739258): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729817 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729817 AND published='1' LIMIT 1
149 (61.988830566406): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729817 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729817 AND published='1' LIMIT 1
150 (!!!!! 1648.1876373291): 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 (54.836273193359): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729817 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729817 AND published='1' LIMIT 1
152 (41.007995605469): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729817 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729817 AND published='1' LIMIT 1
153 (46.014785766602): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294729817 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294729817 AND type='deeppockets_item' AND published='1' LIMIT 1
154 (30.040740966797): 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=213 or channel_id is null)
155 (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=213 or channel_id is null)
156 (28.848648071289): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1
157 (65.803527832031): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729817 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729817 AND published='1' LIMIT 1
158 (46.968460083008): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729817 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729817 AND published='1' LIMIT 1
159 (56.028366088867): select jos_twitters.link from jos_twitters where cat=10
160 (53.882598876953): select jos_facebook.link from jos_facebook where cat=10
161 (60.081481933594): select jos_google_plus.link from jos_google_plus where cat=10
162 (62.942504882812): select jos_linkedin.link from jos_linkedin where cat=10