2026-07-22T01:50:11Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/161332024-11-29T17:16:47Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Mulero, Francisca
author
Oteo, Marta
author
Garaulet, Guillermo
author
Magro, Natalia
author
Rebollo, Lluvia
author
Medrano, Guillermo
author
Campos Olivas, Ramon
author
Santiveri, Clara
author
Sellek, Ricela E
author
Margolles, Yago
author
Arroyo, Alicia G
author
Fernández, Luis Angel
author
Morcillo, Miguel Angel
author
Martinez Torrecuadrada, Jorge Luis
funder
Fundación BBVA
2023-06-01T11:39:00Z
2023-06-01T11:39:00Z
2022-11-24
Front Med (Lausanne). 2022 ;9:1058455.
10.3389/fmed.2022.1058455
2296-858X
Frontiers in medicine
36507540
http://hdl.handle.net/20.500.12105/16133
Triple-negative breast cancer (TNBC) is characterized by aggressiveness and high rates of metastasis. The identification of relevant biomarkers is crucial to improve outcomes for TNBC patients. Membrane type 1-matrix metalloproteinase (MT1-MMP) could be a good candidate because its expression has been reported to correlate with tumor malignancy, progression and metastasis. Moreover, single-domain variable regions (VHHs or Nanobodies) derived from camelid heavy-chain-only antibodies have demonstrated improvements in tissue penetration and blood clearance, important characteristics for cancer imaging. Here, we have developed a nanobody-based PET imaging strategy for TNBC detection that targets MT1-MMP. A llama-derived library was screened against the catalytic domain of MT1-MMP and a panel of specific nanobodies were identified. After a deep characterization, two nanobodies were selected to be labeled with gallium-68 (68Ga). ImmunoPET imaging with both ([68Ga]Ga-NOTA-3TPA14 and [68Ga]Ga-NOTA-3CMP75) in a TNBC mouse model showed precise tumor-targeting capacity in vivo with high signal-to-background ratios. (68Ga)Ga-NOTA-3CMP75 exhibited higher tumor uptake compared to (68Ga)Ga-NOTA-3TPA14. Furthermore, imaging data correlated perfectly with the immunohistochemistry staining results. In conclusion, we found a promising candidate for nanobody-based PET imaging to be further investigated as a diagnostic tool in TNBC.
eng
immunoPET
MT1-MMP
NANOBODIES
GALIUM-68
TNBC (Triple negative breast cancer)
Development of anti-membrane type 1-matrix metalloproteinase nanobodies as immunoPET probes for triple negative breast cancer imaging.
journal article
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