Prostate-specific membrane antigen-targeted radionuclide therapy as a novel therapeutic approach in a syngeneic immunocompetent murine model for oral squamous cell carcinoma
- Author
- Michaël Henrotte (UGent) , David Creytens (UGent) , Filip De Vos (UGent) , Benedicte Descamps (UGent) , Lindsey Devisscher (UGent) , Wouter Huvenne (UGent) , Ken Kersemans (UGent) , Sara Neyt (UGent) , Christian Vanhove (UGent) and Jens Debacker (UGent)
- Organization
- Project
- Abstract
- Aim/Introduction: The prostate-specific membrane antigen (PSMA) is a clinically implemented target for patients with metastatic castration-resistant prostate cancer. However, its expression on tumour-associated neovasculature also makes PSMA a promising target in other malignancies, such as oral squamous cell carcinoma (OSCC). We aimed to assess the effects of PSMA-targeted radionuclide therapy (TRNT) with [177Lu] Lu-PSMA-I&T on tumour growth in a syngeneic orthotopic immunocompetent murine model for OSCC. Materials and Methods: MOC-1 oral squamous carcinoma cells were cultured and injected (7.5 × 105 in a 15 μL DMEM/15 μL Corning® Matrigel® Matrix mixture) into the left anterior lateral tongue of adult male C57BL/6J mice (n = 13). Eleven days after inoculation, mice within the treatment group (n = 5) received a mean (± SD) single intravenous dose of 152 ± 6 MBq [177Lu]Lu-PSMA-I&T in ≤ 200 μL; animals in the control group (n = 8) received 200 μL of phosphatebuffered saline intravenously. Animals were weighed and caliper measurements-based tumour volumes were calculated twice weekly during 5 weeks. After sacrification, formalin-fixed, paraffin-embedded tumour tissue sections were stained with haematoxylin-eosin and immunohistochemically evaluated for PSMA and endothelial marker CD31. Growth rates were calculated between sequential volume measurements, and between each volume measurement and baseline volume. Results: In the group treated with [177Lu]Lu-PSMA-I&T, tumour growth was initially restained, with a significantly lower mean volume compared to the control group 4 days after treatment (p = 0.039). In the treatment group, mean volume initially decreased and was significantly lower 6 days after treatment (p = 0.042). The suppressive effect on tumour growth stagnated one week after treatment, whereafter mean volume increased again. However, mean volume remained significantly lower (p = 0.012-0.040) in the treatment group until 30 days after treatment. Growth rates based on sequential volume measurements did not differ significantly between the two groups, but growth rates based on volume measurements compared to baseline did between 10-21 days after treatment (p= 0.003-0.015). Conclusion: This study is the first to investigate the effects of PSMA-TRNT in an immunocompetent murine model for orthotopically induced OSCC. Our results suggest that a single intravenous dose of c. 150 MBq [177Lu]Lu-PSMA-I&T not only temporarily impeded tumour growth, but also decreased tumour volume in the MOC-1 model. This highlights the potential of PSMA as a novel target for TRNT in mice with OSCC, and advocates further trials with radionuclide therapy in OSCC with regards to dosage and regimen optimisation.
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Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01JR3HWSVK43E8ZAARES4PW0ZJ
- MLA
- Henrotte, Michaël, et al. “Prostate-Specific Membrane Antigen-Targeted Radionuclide Therapy as a Novel Therapeutic Approach in a Syngeneic Immunocompetent Murine Model for Oral Squamous Cell Carcinoma.” EANM’24 : 37th Annual Congress of the European Association of Nuclear Medicine, 2024.
- APA
- Henrotte, M., Creytens, D., De Vos, F., Descamps, B., Devisscher, L., Huvenne, W., … Debacker, J. (2024). Prostate-specific membrane antigen-targeted radionuclide therapy as a novel therapeutic approach in a syngeneic immunocompetent murine model for oral squamous cell carcinoma. EANM’24 : 37th Annual Congress of the European Association of Nuclear Medicine. Presented at the EANM’24 : 37th Annual Congress of the European Association of Nuclear Medicine, Hamburg, Germany.
- Chicago author-date
- Henrotte, Michaël, David Creytens, Filip De Vos, Benedicte Descamps, Lindsey Devisscher, Wouter Huvenne, Ken Kersemans, Sara Neyt, Christian Vanhove, and Jens Debacker. 2024. “Prostate-Specific Membrane Antigen-Targeted Radionuclide Therapy as a Novel Therapeutic Approach in a Syngeneic Immunocompetent Murine Model for Oral Squamous Cell Carcinoma.” In EANM’24 : 37th Annual Congress of the European Association of Nuclear Medicine.
- Chicago author-date (all authors)
- Henrotte, Michaël, David Creytens, Filip De Vos, Benedicte Descamps, Lindsey Devisscher, Wouter Huvenne, Ken Kersemans, Sara Neyt, Christian Vanhove, and Jens Debacker. 2024. “Prostate-Specific Membrane Antigen-Targeted Radionuclide Therapy as a Novel Therapeutic Approach in a Syngeneic Immunocompetent Murine Model for Oral Squamous Cell Carcinoma.” In EANM’24 : 37th Annual Congress of the European Association of Nuclear Medicine.
- Vancouver
- 1.Henrotte M, Creytens D, De Vos F, Descamps B, Devisscher L, Huvenne W, et al. Prostate-specific membrane antigen-targeted radionuclide therapy as a novel therapeutic approach in a syngeneic immunocompetent murine model for oral squamous cell carcinoma. In: EANM’24 : 37th Annual Congress of the European Association of Nuclear Medicine. 2024.
- IEEE
- [1]M. Henrotte et al., “Prostate-specific membrane antigen-targeted radionuclide therapy as a novel therapeutic approach in a syngeneic immunocompetent murine model for oral squamous cell carcinoma,” in EANM’24 : 37th Annual Congress of the European Association of Nuclear Medicine, Hamburg, Germany, 2024.
@inproceedings{01JR3HWSVK43E8ZAARES4PW0ZJ,
abstract = {{Aim/Introduction: The prostate-specific membrane antigen (PSMA) is a clinically implemented target for patients with metastatic castration-resistant prostate cancer. However, its expression on tumour-associated neovasculature also makes PSMA a promising target in other malignancies, such as oral squamous cell carcinoma (OSCC). We aimed to assess the effects of PSMA-targeted radionuclide therapy (TRNT) with [177Lu] Lu-PSMA-I&T on tumour growth in a syngeneic orthotopic immunocompetent murine model for OSCC. Materials and Methods: MOC-1 oral squamous carcinoma cells were cultured and injected (7.5 × 105 in a 15 μL DMEM/15 μL Corning® Matrigel® Matrix mixture) into the left anterior lateral tongue of adult male C57BL/6J mice (n = 13). Eleven days after inoculation, mice within the treatment group (n = 5) received a mean (± SD) single intravenous dose of 152 ± 6 MBq [177Lu]Lu-PSMA-I&T in ≤ 200 μL; animals in the control group (n = 8) received 200 μL of phosphatebuffered saline intravenously. Animals were weighed and caliper measurements-based tumour volumes were calculated twice weekly during 5 weeks. After sacrification, formalin-fixed, paraffin-embedded tumour tissue sections were stained with haematoxylin-eosin and immunohistochemically evaluated for PSMA and endothelial marker CD31. Growth rates were calculated between sequential volume measurements, and between each volume measurement and baseline volume. Results: In the group treated with [177Lu]Lu-PSMA-I&T, tumour growth was initially restained, with a significantly lower mean volume compared to the control group 4 days after treatment (p = 0.039). In the treatment group, mean volume initially decreased and was significantly lower 6 days after treatment (p = 0.042). The suppressive effect on tumour growth stagnated one week after treatment, whereafter mean volume increased again. However, mean volume remained significantly lower (p = 0.012-0.040) in the treatment group until 30 days after treatment. Growth rates based on sequential volume measurements did not differ significantly between the two groups, but growth rates based on volume measurements compared to baseline did between 10-21 days after treatment (p= 0.003-0.015). Conclusion: This study is the first to investigate the effects of PSMA-TRNT in an immunocompetent murine model for orthotopically induced OSCC. Our results suggest that a single intravenous dose of c. 150 MBq [177Lu]Lu-PSMA-I&T not only temporarily impeded tumour growth, but also decreased tumour volume in the MOC-1 model. This highlights the potential of PSMA as a novel target for TRNT in mice with OSCC, and advocates further trials with radionuclide therapy in OSCC with regards to dosage and regimen optimisation.}},
author = {{Henrotte, Michaël and Creytens, David and De Vos, Filip and Descamps, Benedicte and Devisscher, Lindsey and Huvenne, Wouter and Kersemans, Ken and Neyt, Sara and Vanhove, Christian and Debacker, Jens}},
booktitle = {{EANM'24 : 37th Annual Congress of the European Association of Nuclear Medicine}},
language = {{eng}},
location = {{Hamburg, Germany}},
title = {{Prostate-specific membrane antigen-targeted radionuclide therapy as a novel therapeutic approach in a syngeneic immunocompetent murine model for oral squamous cell carcinoma}},
year = {{2024}},
}