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Synthesis and preclinical evaluation of the 99mTc-/177Lu-CXCR4-L theranostic pair for in vivo chemokine-4 receptor-specific targeting

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Abstract

This research aimed to prepare 99mTc-/177Lu-CXCR4-L radiotracers and evaluate their in vitro and in vivo capability to detect the chemokine-4 receptor. Molecular docking calculations, Kd values (< 10 nM) of 99mTc-/177Lu-CXCR4-L (radiochemical purities > 98.5%) estimated by saturation binding assays, as well as biodistribution studies in mice with induced tumors, confirmed the affinity of radiotracers towards CXCR4, expressed in DU-4475 breast cancer cells and C6 glioblastoma cells. Micro-SPECT/CT images showed that 99mTc-CXCR4-L and 177Lu-CXCR4-L could work as a theranostic pair for CXCR4 targets. Results warrant additional research to assess the therapeutic efficacy and dosimetry of 177Lu-CXCR4-L.

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Acknowledgements

This research received financial support from the Mexican National Council of Science and Technology (CONACyT-Mexico, Grant CB2017-2018-A1-S-36841). This work was performed as part of the activities of the ‘‘Laboratorio Nacional de Investigación y Desarrollo de Radiofármacos, CONACyT’’.

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Authors and Affiliations

  1. Departamento de Materiales Radiactivos, Instituto Nacional de Investigaciones Nucleares, 52750, Ocoyoacac, Estado de México, Mexico

    Marcela Ávila-Sánchez, Guillermina Ferro-Flores, Blanca Ocampo-García, Gerardo Bravo-Villegas, Myrna Luna-Gutiérrez, Clara Santos-Cuevas & Erika Azorín-Vega

  2. Programa de Doctorado en Ciencias de la Salud, Universidad Autónoma del Estado de México, 50180, Toluca, Estado de México, Mexico

    Marcela Ávila-Sánchez & Gerardo Bravo-Villegas

  3. CONACyT, Instituto Nacional de Investigaciones Nucleares, 52750, Ocoyoacac, Estado de México, Mexico

    Nallely Jiménez-Mancilla

  4. Facultad de Medicina, Universidad Autónoma del Estado de México, 50180, Toluca, Estado de México, Mexico

    Liliana Aranda-Lara & Keila Isaac-Olivé

  5. Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128, Padua, Italy

    Laura Melendez-Alafort

Authors
  1. Marcela Ávila-Sánchez
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  2. Guillermina Ferro-Flores
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  6. Myrna Luna-Gutiérrez
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  7. Clara Santos-Cuevas
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  11. Laura Melendez-Alafort
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Corresponding authors

Correspondence to Guillermina Ferro-Flores or Nallely Jiménez-Mancilla.

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Conflict of interest

The authors declare no potential conflicts of interest with regard to the research, authorship, and/or publication of this article.

Ethical approval

All applicable international, national and/or institutional guidelines for the care and use of animals were followed. This research was approved by the CICUAL-ININ Ethics Committee (Internal Committee of Care and Use of Laboratory Animals of the National Institute of Nuclear Research, Approval No. 02-2018).

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Ávila-Sánchez, M., Ferro-Flores, G., Jiménez-Mancilla, N. et al. Synthesis and preclinical evaluation of the 99mTc-/177Lu-CXCR4-L theranostic pair for in vivo chemokine-4 receptor-specific targeting. J Radioanal Nucl Chem 324, 21–32 (2020). https://doi.org/10.1007/s10967-020-07043-6

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  • DOI: https://doi.org/10.1007/s10967-020-07043-6

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