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(99m)Tc-CXCR4-L for Imaging of the Chemokine-4 Receptor Associated with Brain Tumor Invasiveness: Biokinetics, Radiation Dosimetry, and Proof of Concept in Humans

Overexpression of the chemokine-4 receptor (CXCR4) in brain tumors is associated with high cancer cell invasiveness. Recently, we reported the preclinical evaluation of (99m)Tc-CXCR4-L (cyclo-D-Tyr-D-[NMe]Orn[EDDA-(99m)Tc-6-hydrazinylnicotinyl]-Arg-NaI-Gly) as a SPECT radioligand capable of specific...

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Autores principales: Vallejo-Armenta, Paola, Santos-Cuevas, Clara, Soto-Andonaegui, Juan, Villanueva-Pérez, Rosa M., González-Díaz, Jorge I., García-Pérez, Francisco O., Arrellano-Zarate, Angélica, Luna-Gutiérrez, Myrna, Azorín-Vega, Erika, Ocampo-García, Blanca, Ferro-Flores, Guillermina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201577/
https://www.ncbi.nlm.nih.gov/pubmed/32410920
http://dx.doi.org/10.1155/2020/2525037
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author Vallejo-Armenta, Paola
Santos-Cuevas, Clara
Soto-Andonaegui, Juan
Villanueva-Pérez, Rosa M.
González-Díaz, Jorge I.
García-Pérez, Francisco O.
Arrellano-Zarate, Angélica
Luna-Gutiérrez, Myrna
Azorín-Vega, Erika
Ocampo-García, Blanca
Ferro-Flores, Guillermina
author_facet Vallejo-Armenta, Paola
Santos-Cuevas, Clara
Soto-Andonaegui, Juan
Villanueva-Pérez, Rosa M.
González-Díaz, Jorge I.
García-Pérez, Francisco O.
Arrellano-Zarate, Angélica
Luna-Gutiérrez, Myrna
Azorín-Vega, Erika
Ocampo-García, Blanca
Ferro-Flores, Guillermina
author_sort Vallejo-Armenta, Paola
collection PubMed
description Overexpression of the chemokine-4 receptor (CXCR4) in brain tumors is associated with high cancer cell invasiveness. Recently, we reported the preclinical evaluation of (99m)Tc-CXCR4-L (cyclo-D-Tyr-D-[NMe]Orn[EDDA-(99m)Tc-6-hydrazinylnicotinyl]-Arg-NaI-Gly) as a SPECT radioligand capable of specifically detecting the CXCR4 protein. This research aimed to estimate the biokinetic behavior and radiation dosimetry of (99m)Tc-CXCR4-L in healthy subjects, as well as to correlate the radiotracer uptake by brain tumors in patients, with the histological grade of differentiation and CXCR4 expression evaluated by immunohistochemistry. (99m)Tc-CXCR4-L was obtained from freeze-dried kits prepared under GMP conditions (radiochemical purities >97%). Whole-body scans from six healthy volunteers were acquired at 0.3, 1, 2, 4, 6, and 24 h after (99m)Tc-CXCR4-L administration (0.37 GBq). Time-activity curves of different source organs were obtained from the image sequence to adjust the biokinetic models. The OLINDA/EXM code was employed to calculate the equivalent and effective radiation doses. Nine patients with evidence of brain tumor injury (6 primaries and 3 recurrent), determined by MRI, underwent cerebral SPECT at 3 h after administration of (99m)Tc-CXCR4-L (0.74 GBq). Data were expressed as a T/B (tumor uptake/background) ratio. Biopsy examinations included histological grading and anti-CXCR4 immunohistochemistry. Results showed a fast blood activity clearance (T(1/2)α = 0.81 min and T(1/2)β = 12.19 min) with renal and hepatobiliary elimination. The average equivalent doses were 6.10E − 04, 1.41E − 04, and 3.13E − 05 mSv/MBq for the intestine, liver, and kidney, respectively. The effective dose was 3.92E − 03 mSv/MBq. SPECT was positive in 7/9 patients diagnosed as grade II oligodendroglioma (two patients), grade IV glioblastoma (two patients), grade IV gliosarcoma (one patient), metastasis, and diffuse astrocytoma with T/B ratios of 1.3, 2.3, 13, 7, 19, 5.5, and 3.9, respectively, all of them with positive immunohistochemistry. A direct relationship between the grade of differentiation and the expression of CXCR4 was found. The two negative SPECT studies showed negative immunohistochemistry with a diagnosis of reactive gliosis. This “proof-of-concept” research warrants further clinical studies to establish the usefulness of (99m)Tc-CXCR4-L in the diagnosis and prognosis of brain tumors.
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spelling pubmed-72015772020-05-14 (99m)Tc-CXCR4-L for Imaging of the Chemokine-4 Receptor Associated with Brain Tumor Invasiveness: Biokinetics, Radiation Dosimetry, and Proof of Concept in Humans Vallejo-Armenta, Paola Santos-Cuevas, Clara Soto-Andonaegui, Juan Villanueva-Pérez, Rosa M. González-Díaz, Jorge I. García-Pérez, Francisco O. Arrellano-Zarate, Angélica Luna-Gutiérrez, Myrna Azorín-Vega, Erika Ocampo-García, Blanca Ferro-Flores, Guillermina Contrast Media Mol Imaging Research Article Overexpression of the chemokine-4 receptor (CXCR4) in brain tumors is associated with high cancer cell invasiveness. Recently, we reported the preclinical evaluation of (99m)Tc-CXCR4-L (cyclo-D-Tyr-D-[NMe]Orn[EDDA-(99m)Tc-6-hydrazinylnicotinyl]-Arg-NaI-Gly) as a SPECT radioligand capable of specifically detecting the CXCR4 protein. This research aimed to estimate the biokinetic behavior and radiation dosimetry of (99m)Tc-CXCR4-L in healthy subjects, as well as to correlate the radiotracer uptake by brain tumors in patients, with the histological grade of differentiation and CXCR4 expression evaluated by immunohistochemistry. (99m)Tc-CXCR4-L was obtained from freeze-dried kits prepared under GMP conditions (radiochemical purities >97%). Whole-body scans from six healthy volunteers were acquired at 0.3, 1, 2, 4, 6, and 24 h after (99m)Tc-CXCR4-L administration (0.37 GBq). Time-activity curves of different source organs were obtained from the image sequence to adjust the biokinetic models. The OLINDA/EXM code was employed to calculate the equivalent and effective radiation doses. Nine patients with evidence of brain tumor injury (6 primaries and 3 recurrent), determined by MRI, underwent cerebral SPECT at 3 h after administration of (99m)Tc-CXCR4-L (0.74 GBq). Data were expressed as a T/B (tumor uptake/background) ratio. Biopsy examinations included histological grading and anti-CXCR4 immunohistochemistry. Results showed a fast blood activity clearance (T(1/2)α = 0.81 min and T(1/2)β = 12.19 min) with renal and hepatobiliary elimination. The average equivalent doses were 6.10E − 04, 1.41E − 04, and 3.13E − 05 mSv/MBq for the intestine, liver, and kidney, respectively. The effective dose was 3.92E − 03 mSv/MBq. SPECT was positive in 7/9 patients diagnosed as grade II oligodendroglioma (two patients), grade IV glioblastoma (two patients), grade IV gliosarcoma (one patient), metastasis, and diffuse astrocytoma with T/B ratios of 1.3, 2.3, 13, 7, 19, 5.5, and 3.9, respectively, all of them with positive immunohistochemistry. A direct relationship between the grade of differentiation and the expression of CXCR4 was found. The two negative SPECT studies showed negative immunohistochemistry with a diagnosis of reactive gliosis. This “proof-of-concept” research warrants further clinical studies to establish the usefulness of (99m)Tc-CXCR4-L in the diagnosis and prognosis of brain tumors. Hindawi 2020-04-27 /pmc/articles/PMC7201577/ /pubmed/32410920 http://dx.doi.org/10.1155/2020/2525037 Text en Copyright © 2020 Paola Vallejo-Armenta et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Vallejo-Armenta, Paola
Santos-Cuevas, Clara
Soto-Andonaegui, Juan
Villanueva-Pérez, Rosa M.
González-Díaz, Jorge I.
García-Pérez, Francisco O.
Arrellano-Zarate, Angélica
Luna-Gutiérrez, Myrna
Azorín-Vega, Erika
Ocampo-García, Blanca
Ferro-Flores, Guillermina
(99m)Tc-CXCR4-L for Imaging of the Chemokine-4 Receptor Associated with Brain Tumor Invasiveness: Biokinetics, Radiation Dosimetry, and Proof of Concept in Humans
title (99m)Tc-CXCR4-L for Imaging of the Chemokine-4 Receptor Associated with Brain Tumor Invasiveness: Biokinetics, Radiation Dosimetry, and Proof of Concept in Humans
title_full (99m)Tc-CXCR4-L for Imaging of the Chemokine-4 Receptor Associated with Brain Tumor Invasiveness: Biokinetics, Radiation Dosimetry, and Proof of Concept in Humans
title_fullStr (99m)Tc-CXCR4-L for Imaging of the Chemokine-4 Receptor Associated with Brain Tumor Invasiveness: Biokinetics, Radiation Dosimetry, and Proof of Concept in Humans
title_full_unstemmed (99m)Tc-CXCR4-L for Imaging of the Chemokine-4 Receptor Associated with Brain Tumor Invasiveness: Biokinetics, Radiation Dosimetry, and Proof of Concept in Humans
title_short (99m)Tc-CXCR4-L for Imaging of the Chemokine-4 Receptor Associated with Brain Tumor Invasiveness: Biokinetics, Radiation Dosimetry, and Proof of Concept in Humans
title_sort (99m)tc-cxcr4-l for imaging of the chemokine-4 receptor associated with brain tumor invasiveness: biokinetics, radiation dosimetry, and proof of concept in humans
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201577/
https://www.ncbi.nlm.nih.gov/pubmed/32410920
http://dx.doi.org/10.1155/2020/2525037
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