The prostate-specific membrane antigen holds potential as a vascular target for endogenous radiotherapy with [177Lu]Lu-PSMA-I T for triple-negative breast cancer

Abstract Introduction Overexpression of prostate-specific membrane antigen (PSMA) on the vasculature of triple-negative breast cancer (TNBC) presents a promising avenue for targeted endogenous radiotherapy with [177Lu]Lu-PSMA-I&T. This study aimed to assess and compare the therapeutic efficacy o...

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Published in:Breast cancer research : BCR 2024-02, Vol.26 (1), p.1-11
Main Authors: Amelie Heesch, Alexandru Florea, Jochen Maurer, Pardes Habib, Laura S. Werth, Thomas Hansen, Elmar Stickeler, Sabri E. M. Sahnoun, Felix M. Mottaghy, Agnieszka Morgenroth
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Language:English
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Anti-angiogenic therapy
Endogenous radiotherapy
Orthotopic xenograft
Prostate-specific membrane antigen
Triple-negative breast cancer
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container_issue 1
container_start_page 1
container_title Breast cancer research : BCR
container_volume 26
creator Amelie Heesch
Alexandru Florea
Jochen Maurer
Pardes Habib
Laura S. Werth
Thomas Hansen
Elmar Stickeler
Sabri E. M. Sahnoun
Felix M. Mottaghy
Agnieszka Morgenroth
description Abstract Introduction Overexpression of prostate-specific membrane antigen (PSMA) on the vasculature of triple-negative breast cancer (TNBC) presents a promising avenue for targeted endogenous radiotherapy with [177Lu]Lu-PSMA-I&T. This study aimed to assess and compare the therapeutic efficacy of a single dose with a fractionated dose of [177Lu]Lu-PSMA-I&T in an orthotopic model of TNBC. Methods Rj:NMRI-Foxn1 nu/nu mice were used as recipients of MDA-MB-231 xenografts. The single dose group was treated with 1 × 60 ± 5 MBq dose of [177Lu]Lu-PSMA-I&T, while the fractionated dose group received 4 × a 15 ± 2 MBq dose of [177Lu]Lu-PSMA-I&T at 7 day intervals. The control group received 0.9% NaCl. Tumor progression was monitored using [18F]FDG-PET/CT. Ex vivo analysis encompassed immunostaining, TUNEL staining, H&E staining, microautoradiography, and autoradiography. Results Tumor volumes were significantly smaller in the single dose (p 
doi_str_mv 10.1186/s13058-024-01787-9
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Werth ; Thomas Hansen ; Elmar Stickeler ; Sabri E. M. Sahnoun ; Felix M. Mottaghy ; Agnieszka Morgenroth</creator><creatorcontrib>Amelie Heesch ; Alexandru Florea ; Jochen Maurer ; Pardes Habib ; Laura S. Werth ; Thomas Hansen ; Elmar Stickeler ; Sabri E. M. Sahnoun ; Felix M. Mottaghy ; Agnieszka Morgenroth</creatorcontrib><description><![CDATA[Abstract Introduction Overexpression of prostate-specific membrane antigen (PSMA) on the vasculature of triple-negative breast cancer (TNBC) presents a promising avenue for targeted endogenous radiotherapy with [177Lu]Lu-PSMA-I&T. This study aimed to assess and compare the therapeutic efficacy of a single dose with a fractionated dose of [177Lu]Lu-PSMA-I&T in an orthotopic model of TNBC. Methods Rj:NMRI-Foxn1 nu/nu mice were used as recipients of MDA-MB-231 xenografts. The single dose group was treated with 1 × 60 ± 5 MBq dose of [177Lu]Lu-PSMA-I&T, while the fractionated dose group received 4 × a 15 ± 2 MBq dose of [177Lu]Lu-PSMA-I&T at 7 day intervals. The control group received 0.9% NaCl. Tumor progression was monitored using [18F]FDG-PET/CT. Ex vivo analysis encompassed immunostaining, TUNEL staining, H&E staining, microautoradiography, and autoradiography. Results Tumor volumes were significantly smaller in the single dose (p < 0.001) and fractionated dose (p < 0.001) groups. Tumor growth inhibition rates were 38% (single dose) and 30% (fractionated dose). Median survival was notably prolonged in the treated groups compared to the control groups (31d, 28d and 19d for single dose, fractionated dose and control, respectively). [177Lu]Lu-PSMA-I&T decreased the size of viable tumor areas. We further demonstrated, that [177Lu]Lu-PSMA-I&T binds specifically to the tumor-associated vasculature. Conclusion This study highlights the potential of [177Lu]Lu-PSMA-I&T for endogenous radiotherapy of TNBC. Graphical abstract]]></description><identifier>EISSN: 1465-542X</identifier><identifier>DOI: 10.1186/s13058-024-01787-9</identifier><language>eng</language><publisher>BMC</publisher><subject>Anti-angiogenic therapy ; Endogenous radiotherapy ; Orthotopic xenograft ; Prostate-specific membrane antigen ; Triple-negative breast cancer</subject><ispartof>Breast cancer research : BCR, 2024-02, Vol.26 (1), p.1-11</ispartof><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><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Amelie Heesch</creatorcontrib><creatorcontrib>Alexandru Florea</creatorcontrib><creatorcontrib>Jochen Maurer</creatorcontrib><creatorcontrib>Pardes Habib</creatorcontrib><creatorcontrib>Laura S. Werth</creatorcontrib><creatorcontrib>Thomas Hansen</creatorcontrib><creatorcontrib>Elmar Stickeler</creatorcontrib><creatorcontrib>Sabri E. M. Sahnoun</creatorcontrib><creatorcontrib>Felix M. Mottaghy</creatorcontrib><creatorcontrib>Agnieszka Morgenroth</creatorcontrib><title>The prostate-specific membrane antigen holds potential as a vascular target for endogenous radiotherapy with [177Lu]Lu-PSMA-I T for triple-negative breast cancer</title><title>Breast cancer research : BCR</title><description><![CDATA[Abstract Introduction Overexpression of prostate-specific membrane antigen (PSMA) on the vasculature of triple-negative breast cancer (TNBC) presents a promising avenue for targeted endogenous radiotherapy with [177Lu]Lu-PSMA-I&T. This study aimed to assess and compare the therapeutic efficacy of a single dose with a fractionated dose of [177Lu]Lu-PSMA-I&T in an orthotopic model of TNBC. Methods Rj:NMRI-Foxn1 nu/nu mice were used as recipients of MDA-MB-231 xenografts. The single dose group was treated with 1 × 60 ± 5 MBq dose of [177Lu]Lu-PSMA-I&T, while the fractionated dose group received 4 × a 15 ± 2 MBq dose of [177Lu]Lu-PSMA-I&T at 7 day intervals. The control group received 0.9% NaCl. Tumor progression was monitored using [18F]FDG-PET/CT. Ex vivo analysis encompassed immunostaining, TUNEL staining, H&E staining, microautoradiography, and autoradiography. Results Tumor volumes were significantly smaller in the single dose (p < 0.001) and fractionated dose (p < 0.001) groups. Tumor growth inhibition rates were 38% (single dose) and 30% (fractionated dose). Median survival was notably prolonged in the treated groups compared to the control groups (31d, 28d and 19d for single dose, fractionated dose and control, respectively). [177Lu]Lu-PSMA-I&T decreased the size of viable tumor areas. We further demonstrated, that [177Lu]Lu-PSMA-I&T binds specifically to the tumor-associated vasculature. Conclusion This study highlights the potential of [177Lu]Lu-PSMA-I&T for endogenous radiotherapy of TNBC. 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Mottaghy</creatorcontrib><creatorcontrib>Agnieszka Morgenroth</creatorcontrib><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Breast cancer research : BCR</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Amelie Heesch</au><au>Alexandru Florea</au><au>Jochen Maurer</au><au>Pardes Habib</au><au>Laura S. Werth</au><au>Thomas Hansen</au><au>Elmar Stickeler</au><au>Sabri E. M. Sahnoun</au><au>Felix M. Mottaghy</au><au>Agnieszka Morgenroth</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The prostate-specific membrane antigen holds potential as a vascular target for endogenous radiotherapy with [177Lu]Lu-PSMA-I T for triple-negative breast cancer</atitle><jtitle>Breast cancer research : BCR</jtitle><date>2024-02-01</date><risdate>2024</risdate><volume>26</volume><issue>1</issue><spage>1</spage><epage>11</epage><pages>1-11</pages><eissn>1465-542X</eissn><abstract><![CDATA[Abstract Introduction Overexpression of prostate-specific membrane antigen (PSMA) on the vasculature of triple-negative breast cancer (TNBC) presents a promising avenue for targeted endogenous radiotherapy with [177Lu]Lu-PSMA-I&T. This study aimed to assess and compare the therapeutic efficacy of a single dose with a fractionated dose of [177Lu]Lu-PSMA-I&T in an orthotopic model of TNBC. Methods Rj:NMRI-Foxn1 nu/nu mice were used as recipients of MDA-MB-231 xenografts. The single dose group was treated with 1 × 60 ± 5 MBq dose of [177Lu]Lu-PSMA-I&T, while the fractionated dose group received 4 × a 15 ± 2 MBq dose of [177Lu]Lu-PSMA-I&T at 7 day intervals. The control group received 0.9% NaCl. Tumor progression was monitored using [18F]FDG-PET/CT. Ex vivo analysis encompassed immunostaining, TUNEL staining, H&E staining, microautoradiography, and autoradiography. Results Tumor volumes were significantly smaller in the single dose (p < 0.001) and fractionated dose (p < 0.001) groups. Tumor growth inhibition rates were 38% (single dose) and 30% (fractionated dose). Median survival was notably prolonged in the treated groups compared to the control groups (31d, 28d and 19d for single dose, fractionated dose and control, respectively). [177Lu]Lu-PSMA-I&T decreased the size of viable tumor areas. We further demonstrated, that [177Lu]Lu-PSMA-I&T binds specifically to the tumor-associated vasculature. Conclusion This study highlights the potential of [177Lu]Lu-PSMA-I&T for endogenous radiotherapy of TNBC. Graphical abstract]]></abstract><pub>BMC</pub><doi>10.1186/s13058-024-01787-9</doi><oa>free_for_read</oa></addata></record>
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subjects Anti-angiogenic therapy
Endogenous radiotherapy
Orthotopic xenograft
Prostate-specific membrane antigen
Triple-negative breast cancer
title The prostate-specific membrane antigen holds potential as a vascular target for endogenous radiotherapy with [177Lu]Lu-PSMA-I T for triple-negative breast cancer
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