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PET Evaluates Effectiveness of Novel Breast Cancer Treatment

By MedImaging International staff writers
Posted on 28 Jul 2009
A new study revealed that positron emission tomography (PET) scans of laboratory mice can be used to determine whether an innovative type of breast cancer treatment is working as intended.

Researchers effectively used PET and a specially-developed radioactive compound to image HER2--a protein frequently associated with aggressive breast cancer--in breast cancer cells before and after treatment aimed at decreasing HER2 expression. This molecular imaging methodology could facilitate development of new targeted therapies not only for breast cancer, but also for certain types of ovarian, prostate, and lung cancers that may be aggravated due to HER2. The study published in the July 2009 issue of The Journal of Nuclear Medicine (JNM).

"Obtaining an accurate assessment of the HER2 expression levels in breast cancer tumors is absolutely essential to know whether treatment aimed at reduction of the protein levels in tumor cells is effective,” said Dr. Jacek Capala, senior author of the study and investigator for the radiation oncology branch of the U.S. National Cancer Institute (NCI), part of the National Institutes of Health (NIH; Bethesda, MD, USA). "Our study indicates that PET could be a powerful tool both to identify patients who might benefit from targeted molecular therapies and to manage their care by measuring response to treatment. As research into HER2 therapies continues, similar techniques could be developed for other cancers overexpressing different proteins.”

Much new research has been focused on developing therapies targeted to HER2. This protein is overexpressed in approximately 20% of breast cancers and also in some ovarian, prostate, and lung cancers. Tumors that have an overabundance of HER2 protein are more aggressive and more likely to recur than tumors that do not overexpress the protein.

The imaging technique developed in the study represents a breakthrough in measuring HER2 expression. The traditional method requires biopsies of tumors that have been removed from the body; however, these samples may not represent the overall characteristics of the tumor and may not accurately estimate HER2 expression. Moreover, there are currently no means to evaluate how long a therapeutic agent takes to affect the targeted tumors and how long the effects last.

In the study, researchers attached the radioactive nuclide flourine-18 to a HER2-binding variant of a small protein known as an Affibody molecule. PET scans can detect the Affibody compound and allow researchers to visualize breast cancer tumors with HER2 protein in mice. These molecules can also be modified to specifically bind to other targets for cancer diagnosis and therapy.

The researchers implanted human breast cancer cells--expressing either very high or high levels of HER2--under the skin of mice to show that this method of imaging can be used to monitor changes in HER2 expression after treatment. Researchers then intravenously injected the HER2-targeting Affibody compound and performed PET imaging three to five weeks after tumors had formed. Four doses of the drug 17-DMAG were administered, which decreases HER2 expression, spaced 12 hours apart. PET scans were performed before the treatment and after each dose.

The researchers found that HER2 expression was reduced by 71% in mice bearing tumors with very high levels of HER2 protein and by 33% in mice bearing tumors with high levels of the protein, compared to the levels measured before treatment and to tumors that did not receive the treatment. Researchers confirmed their data using established laboratory methods to determine the concentrations of HER2 proteins in the same tumors after they were removed from the mice.

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96 (34.093856811523): SELECT show_live FROM jos_com_show_setting LIMIT 1
97 (25.98762512207): SELECT show_live FROM jos_com_show_setting LIMIT 1
98 (24.795532226562): SELECT show_live FROM jos_com_show_setting LIMIT 1
99 (25.98762512207): SELECT show_live FROM jos_com_show_setting LIMIT 1
100 (25.033950805664): SELECT show_live FROM jos_com_show_setting LIMIT 1
101 (26.226043701172): SELECT show_live FROM jos_com_show_setting LIMIT 1
102 (25.033950805664): SELECT show_live FROM jos_com_show_setting LIMIT 1
103 (25.98762512207): SELECT show_live FROM jos_com_show_setting LIMIT 1
104 (!!!!! 2804.0409088135): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724620 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724620 AND published='1' LIMIT 1
105 (93.936920166016): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724620 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724620 AND published='1' LIMIT 1
106 (55.074691772461): 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=294724620 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
107 (56.982040405273): 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=294724620 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
108 (109.91096496582): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724620 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724620 AND published='1' LIMIT 1
109 (45.061111450195): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724620 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724620 AND published='1' LIMIT 1
110 (46.968460083008): 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=294724620 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
111 (584.12551879883): 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=294724620 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
112 (!!!!! 1724.0047454834): 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 (374.07875061035): 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 (81.062316894531): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724620 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724620 AND published='1' LIMIT 1
115 (86.069107055664): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724620 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724620 AND published='1' LIMIT 1
116 (66.041946411133): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724620 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724620 AND published='1' LIMIT 1
117 (40.054321289062): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724620 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724620 AND published='1' LIMIT 1
118 (48.87580871582): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724620 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724620 AND published='1' LIMIT 1
119 (46.968460083008): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724620 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724620 AND published='1' LIMIT 1
120 (42.915344238281): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724620 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724620 AND published='1' LIMIT 1
121 (36.001205444336): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724620 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724620 AND published='1' LIMIT 1
122 (322.10350036621): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`
123 (!!!!! 19834.995269775): 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 (733.85238647461): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294724620 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294724620 AND type='deeppockets_item' AND published='1' LIMIT 1
125 (!!!!! 8602.1423339844): ( 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 (76.055526733398): ( 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 (44.107437133789): 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 (56.982040405273): 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 (29.087066650391): 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 (323.05717468262): 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 (37.908554077148): 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 (30.040740966797): 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 (611.0668182373): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724620 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
136 (491.14227294922): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724620 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
137 (352.85949707031): SELECT name FROM jos_deeppockets WHERE id=213
138 (52.928924560547): SELECT name FROM jos_deeppockets WHERE id=213
139 (771.99935913086): 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((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
140 (709.05685424805): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))213((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
141 (77.009201049805): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724620 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724620 AND published='1' LIMIT 1
142 (54.121017456055): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724620 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724620 AND published='1' LIMIT 1
143 (!!!!! 7768.8694000244): TRUNCATE TABLE jos_trademed_module
144 (102.04315185547): 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=294724620 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
145 (83.208084106445): 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=294724620 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
146 (890.97023010254): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724620 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
147 (72.956085205078): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724620 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
148 (102.99682617188): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724620 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724620 AND published='1' LIMIT 1
149 (107.0499420166): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724620 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724620 AND published='1' LIMIT 1
150 (!!!!! 1296.0433959961): 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 (61.988830566406): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724620 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724620 AND published='1' LIMIT 1
152 (46.968460083008): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724620 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724620 AND published='1' LIMIT 1
153 (41.007995605469): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294724620 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294724620 AND type='deeppockets_item' AND published='1' LIMIT 1
154 (38.14697265625): 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 (32.186508178711): 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 (34.093856811523): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1
157 (61.988830566406): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724620 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724620 AND published='1' LIMIT 1
158 (46.968460083008): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724620 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724620 AND published='1' LIMIT 1
159 (36.954879760742): select jos_twitters.link from jos_twitters where cat=10
160 (30.994415283203): select jos_facebook.link from jos_facebook where cat=10
161 (31.948089599609): select jos_google_plus.link from jos_google_plus where cat=10
162 (30.994415283203): select jos_linkedin.link from jos_linkedin where cat=10