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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Bibliographic Details
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
Format: Article
Language:English
Subjects:
Anti-angiogenic therapy
Endogenous radiotherapy
Orthotopic xenograft
Prostate-specific membrane antigen
Triple-negative breast cancer
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Summary: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 
ISSN:1465-542X
DOI:10.1186/s13058-024-01787-9