TY - JOUR
T1 - 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
AU - Heesch, Amelie
AU - Florea, Alexandru
AU - Maurer, Jochen
AU - Habib, Pardes
AU - Werth, Laura S.
AU - Hansen, Thomas
AU - Stickeler, Elmar
AU - Sahnoun, Sabri E.M.
AU - Mottaghy, Felix M.
AU - Morgenroth, Agnieszka
N1 - Funding Information:
Open Access funding enabled and organized by Projekt DEAL. This research was funded by Deutsche Krebshilfe (Project Number: 70113779 and 70113780) and Deutsche Forschungsgemeinschaft in the framework of the Research Training Group ‘Tumor-targeted Drug Delivery’ (Project Number: 331065168).
Publisher Copyright:
© The Author(s) 2024.
PY - 2024/2
Y1 - 2024/2
N2 - 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. Graphical abstract: (Figure presented.)
AB - 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. Graphical abstract: (Figure presented.)
KW - Anti-angiogenic therapy
KW - Endogenous radiotherapy
KW - Orthotopic xenograft
KW - Prostate-specific membrane antigen
KW - Triple-negative breast cancer
U2 - 10.1186/s13058-024-01787-9
DO - 10.1186/s13058-024-01787-9
M3 - Article
SN - 1465-5411
VL - 26
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 1
M1 - 30
ER -