Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/16133
Título
Development of anti-membrane type 1-matrix metalloproteinase nanobodies as immunoPET probes for triple negative breast cancer imaging.
Autor(es)
Mulero, Francisca CNIO | Oteo, Marta | Garaulet, Guillermo | Magro, Natalia | Rebollo, Lluvia | Medrano, Guillermo | Campos Olivas, Ramon CNIO | Santiveri, Clara | Sellek, Ricela E | Margolles, Yago | Arroyo, Alicia G CNIC | Fernández, Luis Angel | Morcillo, Miguel Angel | Martinez Torrecuadrada, Jorge Luis CNIO
Fecha de publicación
2022-11-24
Cita
Front Med (Lausanne). 2022 ;9:1058455.
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
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