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

Marcela Ávila-Sánchez; Guillermina Ferro-Flores; Nallely Jiménez-Mancilla; Blanca Ocampo-García; Gerardo Bravo-Villegas; Myrna Luna-Gutiérrez; Clara Santos-Cuevas; Erika Azorín-Vega; Liliana Aranda-Lara; Keila Isaac-Olivé; Laura Melendez-Alafort

doi:10.1007/s10967-020-07043-6

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

Marcela Ávila-Sánchez, Guillermina Ferro-Flores, Nallely Jiménez-Mancilla, Blanca Ocampo-García, Gerardo Bravo-Villegas, Myrna Luna-Gutiérrez, Clara Santos-Cuevas, Erika Azorín-Vega, Liliana Aranda-Lara, Keila Isaac-Olivé, Laura Melendez-Alafort

Istituto Oncologico Veneto

Research output: Contribution to journal › Article › peer-review

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, K_d 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.

Original language	English
Pages (from-to)	21-32
Number of pages	12
Journal	Journal of Radioanalytical and Nuclear Chemistry
Volume	324
Issue number	1
DOIs	https://doi.org/10.1007/s10967-020-07043-6
Publication status	Published - Apr 1 2020

Keywords

Lu-CXCR4-L
Tc-CXCR4-L
Chemokine-4 receptor
DOTA-HYNIC-CXCR4-L
HYNIC-CXCR4-L
Theranostic pair

ASJC Scopus subject areas

Analytical Chemistry
Nuclear Energy and Engineering
Radiology Nuclear Medicine and imaging
Pollution
Spectroscopy
Public Health, Environmental and Occupational Health
Health, Toxicology and Mutagenesis

Access to Document

10.1007/s10967-020-07043-6

Cite this

Ávila-Sánchez, M., Ferro-Flores, G., Jiménez-Mancilla, N., Ocampo-García, B., Bravo-Villegas, G., Luna-Gutiérrez, M., Santos-Cuevas, C., Azorín-Vega, E., Aranda-Lara, L., Isaac-Olivé, K., & Melendez-Alafort, L. (2020). Synthesis and preclinical evaluation of the ^99mTc-/¹⁷⁷Lu-CXCR4-L theranostic pair for in vivo chemokine-4 receptor-specific targeting. Journal of Radioanalytical and Nuclear Chemistry, 324(1), 21-32. https://doi.org/10.1007/s10967-020-07043-6

Synthesis and preclinical evaluation of the ^99mTc-/¹⁷⁷Lu-CXCR4-L theranostic pair for in vivo chemokine-4 receptor-specific targeting. / Ávila-Sánchez, Marcela; Ferro-Flores, Guillermina; Jiménez-Mancilla, Nallely; Ocampo-García, Blanca; Bravo-Villegas, Gerardo; Luna-Gutiérrez, Myrna; Santos-Cuevas, Clara; Azorín-Vega, Erika; Aranda-Lara, Liliana; Isaac-Olivé, Keila; Melendez-Alafort, Laura.

In: Journal of Radioanalytical and Nuclear Chemistry, Vol. 324, No. 1, 01.04.2020, p. 21-32.

Research output: Contribution to journal › Article › peer-review

Ávila-Sánchez, M, Ferro-Flores, G, Jiménez-Mancilla, N, Ocampo-García, B, Bravo-Villegas, G, Luna-Gutiérrez, M, Santos-Cuevas, C, Azorín-Vega, E, Aranda-Lara, L, Isaac-Olivé, K & Melendez-Alafort, L 2020, 'Synthesis and preclinical evaluation of the ^99mTc-/¹⁷⁷Lu-CXCR4-L theranostic pair for in vivo chemokine-4 receptor-specific targeting', Journal of Radioanalytical and Nuclear Chemistry, vol. 324, no. 1, pp. 21-32. https://doi.org/10.1007/s10967-020-07043-6

Ávila-Sánchez, Marcela ; Ferro-Flores, Guillermina ; Jiménez-Mancilla, Nallely ; Ocampo-García, Blanca ; Bravo-Villegas, Gerardo ; Luna-Gutiérrez, Myrna ; Santos-Cuevas, Clara ; Azorín-Vega, Erika ; Aranda-Lara, Liliana ; Isaac-Olivé, Keila ; Melendez-Alafort, Laura. / Synthesis and preclinical evaluation of the ^99mTc-/¹⁷⁷Lu-CXCR4-L theranostic pair for in vivo chemokine-4 receptor-specific targeting. In: Journal of Radioanalytical and Nuclear Chemistry. 2020 ; Vol. 324, No. 1. pp. 21-32.

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

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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author = "Marcela {\'A}vila-S{\'a}nchez and Guillermina Ferro-Flores and Nallely Jim{\'e}nez-Mancilla and Blanca Ocampo-Garc{\'i}a and Gerardo Bravo-Villegas and Myrna Luna-Guti{\'e}rrez and Clara Santos-Cuevas and Erika Azor{\'i}n-Vega and Liliana Aranda-Lara and Keila Isaac-Oliv{\'e} and Laura Melendez-Alafort",

note = "Funding Information: 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 {\textquoteleft}{\textquoteleft}Laboratorio Nacional de Investigaci{\'o}n y Desarrollo de Radiof{\'a}rmacos, CONACyT{\textquoteright}{\textquoteright}. Publisher Copyright: {\textcopyright} 2020, Akad{\'e}miai Kiad{\'o}, Budapest, Hungary. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

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AU - Ferro-Flores, Guillermina

AU - Jiménez-Mancilla, Nallely

AU - Ocampo-García, Blanca

AU - Bravo-Villegas, Gerardo

AU - Luna-Gutiérrez, Myrna

AU - Santos-Cuevas, Clara

AU - Azorín-Vega, Erika

AU - Aranda-Lara, Liliana

AU - Isaac-Olivé, Keila

AU - Melendez-Alafort, Laura

N1 - Funding Information: 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’’. Publisher Copyright: © 2020, Akadémiai Kiadó, Budapest, Hungary. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/4/1

Y1 - 2020/4/1

N2 - 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.

AB - 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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KW - Theranostic pair

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