OR03-01 Effects Of Alpha-emitting Meta-211At-astato-benzylguanidine (211At-MABG) Compared To 131I-meta-iodobenzylguanidine (131I-MIBG) on Tumor Growth Suppression in a Pheochromocytoma Mouse Model
Objectives: Given the limited treatment approaches currently available for patients with metastatic pheochromocytoma and paraganglioma (PPGL), new effective approaches are being sought. The radioisotope approach using 131I-meta-iodobenzylguanidine (131I-MIBG) has limited survival benefits in metasta...
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| Veröffentlicht in: | Journal of the Endocrine Society 2020-05, Vol.4 (Supplement_1) |
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| creator | Yoshinaga, Keiichiro Zhao, Songji Washino, Komei Aoki, Miho Nishijima, Ken-ichi Shimoyama, Saki Ukon, Naoyuki Gao, Fengying Washiyama, Kohshin Ito, Natsue Yoshioka, Naho Tamura, Naomi Takahashi, Kazuhiro Ito, Hiroshi Higashi, Tatsuya |
| description | Objectives: Given the limited treatment approaches currently available for patients with metastatic pheochromocytoma and paraganglioma (PPGL), new effective approaches are being sought. The radioisotope approach using 131I-meta-iodobenzylguanidine (131I-MIBG) has limited survival benefits in metastatic PPGL but is currently considered one of the standard therapeutic approaches. In theory, the alpha-emitting radiopharmaceutical meta-211At-astato-benzylguanidine (211At-MABG) could be a very effective targeted treatment for metastatic PPGL. However, this possibility has not been evaluated. Therefore, the purpose of this study was to evaluate the tumor growth suppression effects of 211At-MABG compared to 131I-MIBG using a PC-12 mouse pheochromocytoma model.
Methods: Rat pheochromocytoma (PC-12) cells were subcutaneously inoculated into male BALB/c nu/nu nude mice. When tumor volumes reached approximately 300 mm3, mice bearing PC-12 tumors received intravenously either 1.11 MBq of 211At-MABG (n=6), 31 MBq of 131I-MIBG (n=3) or vehicle solvent (n = 6). The tumor volume was measured 3 times per week for 2 weeks. The tumor volume was compared among the three groups.
Results: At 14 days, the tumor volumes significantly increased in the control group (328.82±83.65 to 3568.83±693.23 mm3, P |
| doi_str_mv | 10.1210/jendso/bvaa046.250 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmedcentral_cross</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7208517</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>pubmedcentral_primary_oai_pubmedcentral_nih_gov_7208517</sourcerecordid><originalsourceid>FETCH-LOGICAL-c1420-9392a368b11ffb041cba8dc8e4e0e3f36b389f0f56bde276a1eb8677bff6f99d3</originalsourceid><addsrcrecordid>eNplkU9LIzEYh4dFYcX1C-wpx_UQzZ_p_LkItWi3YKnsds8hmbzpRGaSIcko9fP5wWytyIqXvIGH53d5suwnJReUUXL5AE5Hf6kepSR5ccEm5Ft2wvKSYVqX7Oi___fsLMYHQgiteV7n-Un2svpDOCYU3RgDTYpoZdC0G1qJobcpWbdBS0gSM0qnCcuYZPJYgXvedptROqutA_TrQJfT6_k5mvl-kAE0WntEOV3gfu9br_0X7Q0vF3vLO7Qeex_QPPin1KK_4zAEiNHugHVIovsWfNMG3_tmm3wv0dKPEXavhu5HdmxkF-Hs_Z5m_25v1rPf-G41X8ymd7ihOSO45jWTvKgUpcYoktNGyUo3FeRAgBteKF7VhphJoTSwspAUVFWUpTKmMHWt-Wl2ddgdRtWDbsClIDsxBNvLsBVeWvGZONuKjX8UJSPVhJa7AXYYaIKPMYD5cCkR-5bi0FK8txS7lvwVSBeWzA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>OR03-01 Effects Of Alpha-emitting Meta-211At-astato-benzylguanidine (211At-MABG) Compared To 131I-meta-iodobenzylguanidine (131I-MIBG) on Tumor Growth Suppression in a Pheochromocytoma Mouse Model</title><source>DOAJ Directory of Open Access Journals</source><source>Oxford Journals Open Access Collection</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Yoshinaga, Keiichiro ; Zhao, Songji ; Washino, Komei ; Aoki, Miho ; Nishijima, Ken-ichi ; Shimoyama, Saki ; Ukon, Naoyuki ; Gao, Fengying ; Washiyama, Kohshin ; Ito, Natsue ; Yoshioka, Naho ; Tamura, Naomi ; Takahashi, Kazuhiro ; Ito, Hiroshi ; Higashi, Tatsuya</creator><creatorcontrib>Yoshinaga, Keiichiro ; Zhao, Songji ; Washino, Komei ; Aoki, Miho ; Nishijima, Ken-ichi ; Shimoyama, Saki ; Ukon, Naoyuki ; Gao, Fengying ; Washiyama, Kohshin ; Ito, Natsue ; Yoshioka, Naho ; Tamura, Naomi ; Takahashi, Kazuhiro ; Ito, Hiroshi ; Higashi, Tatsuya</creatorcontrib><description>Objectives: Given the limited treatment approaches currently available for patients with metastatic pheochromocytoma and paraganglioma (PPGL), new effective approaches are being sought. The radioisotope approach using 131I-meta-iodobenzylguanidine (131I-MIBG) has limited survival benefits in metastatic PPGL but is currently considered one of the standard therapeutic approaches. In theory, the alpha-emitting radiopharmaceutical meta-211At-astato-benzylguanidine (211At-MABG) could be a very effective targeted treatment for metastatic PPGL. However, this possibility has not been evaluated. Therefore, the purpose of this study was to evaluate the tumor growth suppression effects of 211At-MABG compared to 131I-MIBG using a PC-12 mouse pheochromocytoma model.
Methods: Rat pheochromocytoma (PC-12) cells were subcutaneously inoculated into male BALB/c nu/nu nude mice. When tumor volumes reached approximately 300 mm3, mice bearing PC-12 tumors received intravenously either 1.11 MBq of 211At-MABG (n=6), 31 MBq of 131I-MIBG (n=3) or vehicle solvent (n = 6). The tumor volume was measured 3 times per week for 2 weeks. The tumor volume was compared among the three groups.
Results: At 14 days, the tumor volumes significantly increased in the control group (328.82±83.65 to 3568.83±693.23 mm3, P<0.001). In contrast, there were no significant changes in tumor volumes in the 211At-MABG group (284.65±56.77 to 274.3±87.95 mm3, P=0.616) and 131I-MIBG group (484.40±46.25 to 323.93±127.27 mm3, P=0.084). The 211At-MABG group showed significantly lower percentage change in tumor volume than did the control group (-5.0±15.99 vs. 1043.83±320.79%, P<0.001), and 131I-MIBG group also showed significant volume reduction rate compared to that of the control group (-34.33±21.39 vs. 1043.82±320.79%, P<0.001). There was no significant difference in percentage tumor volume changes between the 211At-MABG and 131I-MIBG groups (P=0.052). Conclusion: At 14 days after radiopharmaceutical administration, 211At-MABG produced significant tumor volume reduction as compared to that in the control group and to that associated with 131I-MIBG, which is considered one of the current treatment options. Therefore, 211At-MABG may have future clinical applications for the treatment of metastatic pheochromocytoma and paraganglioma.</description><identifier>ISSN: 2472-1972</identifier><identifier>EISSN: 2472-1972</identifier><identifier>DOI: 10.1210/jendso/bvaa046.250</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Adrenal</subject><ispartof>Journal of the Endocrine Society, 2020-05, Vol.4 (Supplement_1)</ispartof><rights>Endocrine Society 2020. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7208517/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7208517/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids></links><search><creatorcontrib>Yoshinaga, Keiichiro</creatorcontrib><creatorcontrib>Zhao, Songji</creatorcontrib><creatorcontrib>Washino, Komei</creatorcontrib><creatorcontrib>Aoki, Miho</creatorcontrib><creatorcontrib>Nishijima, Ken-ichi</creatorcontrib><creatorcontrib>Shimoyama, Saki</creatorcontrib><creatorcontrib>Ukon, Naoyuki</creatorcontrib><creatorcontrib>Gao, Fengying</creatorcontrib><creatorcontrib>Washiyama, Kohshin</creatorcontrib><creatorcontrib>Ito, Natsue</creatorcontrib><creatorcontrib>Yoshioka, Naho</creatorcontrib><creatorcontrib>Tamura, Naomi</creatorcontrib><creatorcontrib>Takahashi, Kazuhiro</creatorcontrib><creatorcontrib>Ito, Hiroshi</creatorcontrib><creatorcontrib>Higashi, Tatsuya</creatorcontrib><title>OR03-01 Effects Of Alpha-emitting Meta-211At-astato-benzylguanidine (211At-MABG) Compared To 131I-meta-iodobenzylguanidine (131I-MIBG) on Tumor Growth Suppression in a Pheochromocytoma Mouse Model</title><title>Journal of the Endocrine Society</title><description>Objectives: Given the limited treatment approaches currently available for patients with metastatic pheochromocytoma and paraganglioma (PPGL), new effective approaches are being sought. The radioisotope approach using 131I-meta-iodobenzylguanidine (131I-MIBG) has limited survival benefits in metastatic PPGL but is currently considered one of the standard therapeutic approaches. In theory, the alpha-emitting radiopharmaceutical meta-211At-astato-benzylguanidine (211At-MABG) could be a very effective targeted treatment for metastatic PPGL. However, this possibility has not been evaluated. Therefore, the purpose of this study was to evaluate the tumor growth suppression effects of 211At-MABG compared to 131I-MIBG using a PC-12 mouse pheochromocytoma model.
Methods: Rat pheochromocytoma (PC-12) cells were subcutaneously inoculated into male BALB/c nu/nu nude mice. When tumor volumes reached approximately 300 mm3, mice bearing PC-12 tumors received intravenously either 1.11 MBq of 211At-MABG (n=6), 31 MBq of 131I-MIBG (n=3) or vehicle solvent (n = 6). The tumor volume was measured 3 times per week for 2 weeks. The tumor volume was compared among the three groups.
Results: At 14 days, the tumor volumes significantly increased in the control group (328.82±83.65 to 3568.83±693.23 mm3, P<0.001). In contrast, there were no significant changes in tumor volumes in the 211At-MABG group (284.65±56.77 to 274.3±87.95 mm3, P=0.616) and 131I-MIBG group (484.40±46.25 to 323.93±127.27 mm3, P=0.084). The 211At-MABG group showed significantly lower percentage change in tumor volume than did the control group (-5.0±15.99 vs. 1043.83±320.79%, P<0.001), and 131I-MIBG group also showed significant volume reduction rate compared to that of the control group (-34.33±21.39 vs. 1043.82±320.79%, P<0.001). There was no significant difference in percentage tumor volume changes between the 211At-MABG and 131I-MIBG groups (P=0.052). Conclusion: At 14 days after radiopharmaceutical administration, 211At-MABG produced significant tumor volume reduction as compared to that in the control group and to that associated with 131I-MIBG, which is considered one of the current treatment options. Therefore, 211At-MABG may have future clinical applications for the treatment of metastatic pheochromocytoma and paraganglioma.</description><subject>Adrenal</subject><issn>2472-1972</issn><issn>2472-1972</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNplkU9LIzEYh4dFYcX1C-wpx_UQzZ_p_LkItWi3YKnsds8hmbzpRGaSIcko9fP5wWytyIqXvIGH53d5suwnJReUUXL5AE5Hf6kepSR5ccEm5Ft2wvKSYVqX7Oi___fsLMYHQgiteV7n-Un2svpDOCYU3RgDTYpoZdC0G1qJobcpWbdBS0gSM0qnCcuYZPJYgXvedptROqutA_TrQJfT6_k5mvl-kAE0WntEOV3gfu9br_0X7Q0vF3vLO7Qeex_QPPin1KK_4zAEiNHugHVIovsWfNMG3_tmm3wv0dKPEXavhu5HdmxkF-Hs_Z5m_25v1rPf-G41X8ymd7ihOSO45jWTvKgUpcYoktNGyUo3FeRAgBteKF7VhphJoTSwspAUVFWUpTKmMHWt-Wl2ddgdRtWDbsClIDsxBNvLsBVeWvGZONuKjX8UJSPVhJa7AXYYaIKPMYD5cCkR-5bi0FK8txS7lvwVSBeWzA</recordid><startdate>20200508</startdate><enddate>20200508</enddate><creator>Yoshinaga, Keiichiro</creator><creator>Zhao, Songji</creator><creator>Washino, Komei</creator><creator>Aoki, Miho</creator><creator>Nishijima, Ken-ichi</creator><creator>Shimoyama, Saki</creator><creator>Ukon, Naoyuki</creator><creator>Gao, Fengying</creator><creator>Washiyama, Kohshin</creator><creator>Ito, Natsue</creator><creator>Yoshioka, Naho</creator><creator>Tamura, Naomi</creator><creator>Takahashi, Kazuhiro</creator><creator>Ito, Hiroshi</creator><creator>Higashi, Tatsuya</creator><general>Oxford University Press</general><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20200508</creationdate><title>OR03-01 Effects Of Alpha-emitting Meta-211At-astato-benzylguanidine (211At-MABG) Compared To 131I-meta-iodobenzylguanidine (131I-MIBG) on Tumor Growth Suppression in a Pheochromocytoma Mouse Model</title><author>Yoshinaga, Keiichiro ; Zhao, Songji ; Washino, Komei ; Aoki, Miho ; Nishijima, Ken-ichi ; Shimoyama, Saki ; Ukon, Naoyuki ; Gao, Fengying ; Washiyama, Kohshin ; Ito, Natsue ; Yoshioka, Naho ; Tamura, Naomi ; Takahashi, Kazuhiro ; Ito, Hiroshi ; Higashi, Tatsuya</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1420-9392a368b11ffb041cba8dc8e4e0e3f36b389f0f56bde276a1eb8677bff6f99d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adrenal</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yoshinaga, Keiichiro</creatorcontrib><creatorcontrib>Zhao, Songji</creatorcontrib><creatorcontrib>Washino, Komei</creatorcontrib><creatorcontrib>Aoki, Miho</creatorcontrib><creatorcontrib>Nishijima, Ken-ichi</creatorcontrib><creatorcontrib>Shimoyama, Saki</creatorcontrib><creatorcontrib>Ukon, Naoyuki</creatorcontrib><creatorcontrib>Gao, Fengying</creatorcontrib><creatorcontrib>Washiyama, Kohshin</creatorcontrib><creatorcontrib>Ito, Natsue</creatorcontrib><creatorcontrib>Yoshioka, Naho</creatorcontrib><creatorcontrib>Tamura, Naomi</creatorcontrib><creatorcontrib>Takahashi, Kazuhiro</creatorcontrib><creatorcontrib>Ito, Hiroshi</creatorcontrib><creatorcontrib>Higashi, Tatsuya</creatorcontrib><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of the Endocrine Society</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yoshinaga, Keiichiro</au><au>Zhao, Songji</au><au>Washino, Komei</au><au>Aoki, Miho</au><au>Nishijima, Ken-ichi</au><au>Shimoyama, Saki</au><au>Ukon, Naoyuki</au><au>Gao, Fengying</au><au>Washiyama, Kohshin</au><au>Ito, Natsue</au><au>Yoshioka, Naho</au><au>Tamura, Naomi</au><au>Takahashi, Kazuhiro</au><au>Ito, Hiroshi</au><au>Higashi, Tatsuya</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>OR03-01 Effects Of Alpha-emitting Meta-211At-astato-benzylguanidine (211At-MABG) Compared To 131I-meta-iodobenzylguanidine (131I-MIBG) on Tumor Growth Suppression in a Pheochromocytoma Mouse Model</atitle><jtitle>Journal of the Endocrine Society</jtitle><date>2020-05-08</date><risdate>2020</risdate><volume>4</volume><issue>Supplement_1</issue><issn>2472-1972</issn><eissn>2472-1972</eissn><abstract>Objectives: Given the limited treatment approaches currently available for patients with metastatic pheochromocytoma and paraganglioma (PPGL), new effective approaches are being sought. The radioisotope approach using 131I-meta-iodobenzylguanidine (131I-MIBG) has limited survival benefits in metastatic PPGL but is currently considered one of the standard therapeutic approaches. In theory, the alpha-emitting radiopharmaceutical meta-211At-astato-benzylguanidine (211At-MABG) could be a very effective targeted treatment for metastatic PPGL. However, this possibility has not been evaluated. Therefore, the purpose of this study was to evaluate the tumor growth suppression effects of 211At-MABG compared to 131I-MIBG using a PC-12 mouse pheochromocytoma model.
Methods: Rat pheochromocytoma (PC-12) cells were subcutaneously inoculated into male BALB/c nu/nu nude mice. When tumor volumes reached approximately 300 mm3, mice bearing PC-12 tumors received intravenously either 1.11 MBq of 211At-MABG (n=6), 31 MBq of 131I-MIBG (n=3) or vehicle solvent (n = 6). The tumor volume was measured 3 times per week for 2 weeks. The tumor volume was compared among the three groups.
Results: At 14 days, the tumor volumes significantly increased in the control group (328.82±83.65 to 3568.83±693.23 mm3, P<0.001). In contrast, there were no significant changes in tumor volumes in the 211At-MABG group (284.65±56.77 to 274.3±87.95 mm3, P=0.616) and 131I-MIBG group (484.40±46.25 to 323.93±127.27 mm3, P=0.084). The 211At-MABG group showed significantly lower percentage change in tumor volume than did the control group (-5.0±15.99 vs. 1043.83±320.79%, P<0.001), and 131I-MIBG group also showed significant volume reduction rate compared to that of the control group (-34.33±21.39 vs. 1043.82±320.79%, P<0.001). There was no significant difference in percentage tumor volume changes between the 211At-MABG and 131I-MIBG groups (P=0.052). Conclusion: At 14 days after radiopharmaceutical administration, 211At-MABG produced significant tumor volume reduction as compared to that in the control group and to that associated with 131I-MIBG, which is considered one of the current treatment options. Therefore, 211At-MABG may have future clinical applications for the treatment of metastatic pheochromocytoma and paraganglioma.</abstract><cop>US</cop><pub>Oxford University Press</pub><doi>10.1210/jendso/bvaa046.250</doi><oa>free_for_read</oa></addata></record> |
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| title | OR03-01 Effects Of Alpha-emitting Meta-211At-astato-benzylguanidine (211At-MABG) Compared To 131I-meta-iodobenzylguanidine (131I-MIBG) on Tumor Growth Suppression in a Pheochromocytoma Mouse Model |
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