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

  • Breast Cancer Res. 2024 Feb 20;26(1):30. doi: 10.1186/s13058-024-01787-9.
Amelie Heesch  1 ,  Alexandru Florea  2  3  4 ,  Jochen Maurer  5  6 ,  Pardes Habib  7 ,  Laura S Werth  2 ,  Thomas Hansen  5 ,  Elmar Stickeler  5  6 ,  Sabri E M Sahnoun  2 ,  Felix M Mottaghy  2  3  6 ,  Agnieszka Morgenroth  2
Affiliations
  • 1. Department of Nuclear Medicine, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany. [email protected].
  • 2. Department of Nuclear Medicine, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany.
  • 3. Department of Radiology and Nuclear Medicine, Maastricht University Medical Center (MUMC+), 6202, Maastricht, The Netherlands.
  • 4. School for Cardiovascular Diseases (CARIM), Maastricht University Medical Center (MUMC+), 6202, Maastricht, The Netherlands.
  • 5. Department of Obstetrics and Gynecology, University Hospital RWTH Aachen, 52074, Aachen, Germany.
  • 6. Center for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf (ABCD), Germany.
  • 7. Department of Neurosurgery, School of Medicine, Stanford University, Stanford, USA.
PMID: 38378689 DOI: 10.1186/s13058-024-01787-9
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-Foxn1nu/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.

Keywords
Anti-angiogenic therapy; Endogenous radiotherapy; Orthotopic xenograft; Prostate-specific membrane antigen; Triple-negative breast cancer.
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