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Double Targeting Ligands Identifies and Treats Prostate Cancer

By MedImaging International staff writers
Posted on 27 Sep 2017

Image: Targeted theranostic therapy using RPS-027 (Photo courtesy of JM Kelly / Weill Cornell Medicine).

A new study describes how a theranostic approach can precisely identify prostate cancer tumors for targeted radiotherapy (RT), while sparing healthy cells and reducing side effects.

Developed by researchers at Weill Cornell Medicine (New York, NY, USA), the new approach utilizes a single molecule designed to bind two proteins with differing affinities--prostate-specific membrane antigen (PSMA) and human serum albumin--in an effort to optimize specific tumor localization and enhance targeted alpha radionuclide therapy. The double targeting ligand, RPS-027, was tested in mouse models of human prostate cancer using the radiohalogen 211At.

The results, as assessed via positron emission tomography/computed tomography (PET/CT), showed high tumor uptake, reduced kidney uptake, and very favorable tissue distribution. When compared to existing ligands proposed for targeted therapy of prostate cancer, RPS-027 has tumor-to-tissue ratios that predicted a significant reduction in side effects during therapy, suggesting that dual targeting ligands could serve as the next-generation radiopharmaceuticals for targeted alpha therapy. The study was published in the September 2017 issue of The Journal of Nuclear Medicine.

“We believe that our double targeting ligands are the first PSMA ligands designed to make use of the blood pool as a ‘safe zone’ reservoir to protect sensitive organs and tissues from off-target effects of alpha irradiation and, simultaneously, to reduce kidney localization, while maintaining excellent tumor targeting,” said senior author Professor John Babich, PhD. “If our strategy can be applied successfully to other therapeutic targeting agents, we could expect an expansion in the use of targeted alpha therapy in the not-too-distant future.”

Targeted alpha-particle therapy is a radionuclide therapy that employs radioactive substances, which undergo alpha decay to treat diseased tissue at close proximity. It has the potential to provide highly targeted treatment, especially to microscopic tumor cells such as in leukemias, lymphomas, gliomas, melanoma, and peritoneal carcinomatosis. Appropriate radionuclides can be chemically bound to a targeting biomolecule, which carries the combined radiopharmaceutical to a specific treatment point.

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70 (485.89706420898): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294770906 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

71 (381.9465637207): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294770906 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

72 (70.095062255859): 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`

73 (73.909759521484): SELECT show_live FROM jos_com_show_setting LIMIT 1

74 (103.95050048828): SELECT show_live FROM jos_com_show_setting LIMIT 1

75 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

76 (31.948089599609): SELECT show_live FROM jos_com_show_setting LIMIT 1

77 (30.994415283203): SELECT show_live FROM jos_com_show_setting LIMIT 1

78 (50.067901611328): SELECT show_live FROM jos_com_show_setting LIMIT 1

79 (32.186508178711): SELECT show_live FROM jos_com_show_setting LIMIT 1

80 (34.093856811523): SELECT show_live FROM jos_com_show_setting LIMIT 1

81 (29.802322387695): SELECT show_live FROM jos_com_show_setting LIMIT 1

82 (31.948089599609): SELECT show_live FROM jos_com_show_setting LIMIT 1

83 (30.040740966797): SELECT show_live FROM jos_com_show_setting LIMIT 1

84 (32.186508178711): SELECT show_live FROM jos_com_show_setting LIMIT 1

85 (!!!!! 3457.0693969727): SELECT show_live FROM jos_com_show_setting LIMIT 1

86 (111.10305786133): SELECT show_live FROM jos_com_show_setting LIMIT 1

87 (108.95729064941): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294770906 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

88 (46.014785766602): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294770906 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

89 (64.849853515625): 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 (399.82795715332): SELECT show_live FROM jos_com_show_setting LIMIT 1

91 (!!!!! 2809.0476989746): SELECT show_live FROM jos_com_show_setting LIMIT 1

92 (!!!!! 8302.9270172119): SELECT show_live FROM jos_com_show_setting LIMIT 1

93 (!!!!! 2456.9034576416): SELECT show_live FROM jos_com_show_setting LIMIT 1

94 (122.0703125): SELECT show_live FROM jos_com_show_setting LIMIT 1

95 (48.87580871582): SELECT show_live FROM jos_com_show_setting LIMIT 1

96 (75.101852416992): SELECT show_live FROM jos_com_show_setting LIMIT 1

97 (41.961669921875): SELECT show_live FROM jos_com_show_setting LIMIT 1

98 (256.06155395508): SELECT show_live FROM jos_com_show_setting LIMIT 1

99 (61.03515625): SELECT show_live FROM jos_com_show_setting LIMIT 1

100 (!!!!! 3323.0781555176): SELECT show_live FROM jos_com_show_setting LIMIT 1

101 (118.01719665527): SELECT show_live FROM jos_com_show_setting LIMIT 1

102 (56.982040405273): SELECT show_live FROM jos_com_show_setting LIMIT 1

103 (88.930130004883): SELECT show_live FROM jos_com_show_setting LIMIT 1

104 (161.88621520996): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294770906 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294770906 AND published='1' LIMIT 1

105 (72.002410888672): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294770906 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294770906 AND published='1' LIMIT 1

106 (165.22407531738): 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=294770906 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

107 (772.95303344727): 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=294770906 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

108 (!!!!! 11094.093322754): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294770906 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294770906 AND published='1' LIMIT 1

109 (167.1314239502): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294770906 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294770906 AND published='1' LIMIT 1

110 (!!!!! 7771.0151672363): 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=294770906 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

111 (!!!!! 3667.8314208984): 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=294770906 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

112 (824.92828369141): 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 (!!!!! 3435.8501434326): 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 (224.82872009277): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294770906 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294770906 AND published='1' LIMIT 1

115 (79.154968261719): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294770906 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294770906 AND published='1' LIMIT 1

116 (105.14259338379): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294770906 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294770906 AND published='1' LIMIT 1

117 (61.988830566406): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294770906 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294770906 AND published='1' LIMIT 1

118 (83.92333984375): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294770906 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294770906 AND published='1' LIMIT 1

119 (59.843063354492): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294770906 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294770906 AND published='1' LIMIT 1

120 (487.08915710449): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`

121 (!!!!! 137141.94297791): 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

122 (174.04556274414): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294770906 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294770906 AND published='1' LIMIT 1

123 (91.075897216797): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294770906 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294770906 AND published='1' LIMIT 1

124 (647.06802368164): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294770906 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294770906 AND type='deeppockets_item' AND published='1' LIMIT 1

125 (!!!!! 938688.99345398): ( 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 (108.95729064941): ( 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 (483.98971557617): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294800513 LIMIT 1

128 (72.956085205078): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294800513 LIMIT 1

129 (436.06758117676): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294800359 LIMIT 1

130 (159.97886657715): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294800359 LIMIT 1

131 (526.90505981445): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294800361 LIMIT 1

132 (125.88500976562): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294800361 LIMIT 1

133 (473.97613525391): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294770906 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

134 (370.97930908203): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294770906 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

135 (199.0795135498): SELECT name FROM jos_deeppockets WHERE id=213

136 (46.014785766602): SELECT name FROM jos_deeppockets WHERE id=213

137 (689.98336791992): 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

138 (679.96978759766): 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

139 (108.00361633301): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294770906 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294770906 AND published='1' LIMIT 1

140 (59.843063354492): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294770906 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294770906 AND published='1' LIMIT 1

141 (!!!!! 8365.1542663574): TRUNCATE TABLE jos_trademed_module

142 (159.02519226074): 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=294770906 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

143 (86.069107055664): 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=294770906 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

144 (952.95906066895): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294770906 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

145 (82.969665527344): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294770906 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

146 (97.036361694336): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294770906 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294770906 AND published='1' LIMIT 1

147 (61.03515625): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294770906 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294770906 AND published='1' LIMIT 1

148 (!!!!! 1605.0338745117): 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

149 (121.8318939209): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294770906 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294770906 AND published='1' LIMIT 1

150 (64.849853515625): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294770906 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294770906 AND published='1' LIMIT 1

151 (65.803527832031): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294770906 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294770906 AND type='deeppockets_item' AND published='1' LIMIT 1

152 (!!!!! 2978.0864715576): 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)

153 (198.1258392334): 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)

154 (84.877014160156): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1

155 (164.98565673828): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294770906 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294770906 AND published='1' LIMIT 1

156 (59.127807617188): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294770906 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294770906 AND published='1' LIMIT 1

157 (181.91337585449): select jos_twitters.link from jos_twitters where cat=10

158 (39.100646972656): select jos_facebook.link from jos_facebook where cat=10

159 (37.193298339844): select jos_google_plus.link from jos_google_plus where cat=10

160 (36.001205444336): select jos_linkedin.link from jos_linkedin where cat=10

161 (412.94097900391): update jos_bannersmanager_banner set impmade=impmade+1 where id in(14615,14202,14203)

162 (!!!!! 1426.9351959229): insert into jos_banners_delta values (14615,'2025-04-30 13:39:03','3.145.180.18','view'),(14202,'2025-04-30 13:39:03','3.145.180.18','view'),(14203,'2025-04-30 13:39:03','3.145.180.18','view')

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