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Preparation and radiolabeling of a lyophilized (kit) formulation of DOTA-rituximab with (90)Y and (111)In for domestic radioimmunotherapy and radioscintigraphy of Non-Hodgkin’s Lymphoma

BACKGROUND: On the basis of results of our previous investigations on (90)Y-DTPA-rituximab and in order to fulfil national demands to radioimmunoconjugates for radioscintigraphy and radioimmunotherapy of Non-Hodgkin’s Lymphoma (NHL), preparation and radiolabeling of a lyophilized formulation (kit) o...

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Autores principales: Gholipour, Nazila, Jalilian, Amir Reza, Khalaj, Ali, Johari-Daha, Fariba, Yavari, Kamal, Sabzevari, Omid, Khanchi, Ali Reza, Akhlaghi, Mehdi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4261883/
https://www.ncbi.nlm.nih.gov/pubmed/25074720
http://dx.doi.org/10.1186/2008-2231-22-58
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author Gholipour, Nazila
Jalilian, Amir Reza
Khalaj, Ali
Johari-Daha, Fariba
Yavari, Kamal
Sabzevari, Omid
Khanchi, Ali Reza
Akhlaghi, Mehdi
author_facet Gholipour, Nazila
Jalilian, Amir Reza
Khalaj, Ali
Johari-Daha, Fariba
Yavari, Kamal
Sabzevari, Omid
Khanchi, Ali Reza
Akhlaghi, Mehdi
author_sort Gholipour, Nazila
collection PubMed
description BACKGROUND: On the basis of results of our previous investigations on (90)Y-DTPA-rituximab and in order to fulfil national demands to radioimmunoconjugates for radioscintigraphy and radioimmunotherapy of Non-Hodgkin’s Lymphoma (NHL), preparation and radiolabeling of a lyophilized formulation (kit) of DOTA-rituximab with (111)In and (90)Y was investigated. METHODS: (111)In and (90)Y with high radiochemical and radionuclide purity were prepared by (112)Cd (p,2n)(111)In nuclear reaction and a locally developed (90)Sr/(90)Y generator, respectively. DOTA-rituximab immunoconjugates were prepared by the reaction of solutions of p-SCN-Bz-DOTA and rituximab in carbonate buffer (pH = 9.5) and the number of DOTA per molecule of conjugates were determined by transchelation reaction between DOTA and arsenaso yttrium(III) complex. DOTA-rituximab immunoconjugates were labeled with (111)In and (90)Y and radioimmunoconjugates were checked for radiochemical purity by chromatography methods and for immunoreactivity by cell-binding assay using Raji cell line. The stability of radiolabeled conjugate with the approximate number of 7 DOTA molecules per one rituximab molecule which was prepared in moderate yield and showed moderate immunoreactivity, compared to two other prepared radioimmunoconjugates, was determined at different time intervals and against EDTA and human serum by chromatography methods and reducing SDS-polyacrylamide gel electrophoresis, respectively. The biodistribution of the selected radioimmunoconjugate in rats was determined by measurement of the radioactivity of different organs after sacrificing the animals by ether asphyxiation. RESULTS: The radioimmunoconjugate with approximate DOTA/rituximab molar ratio of 7 showed stability after 24 h at room temperature, after 96 h at 4°C, as the lyophilized formulation after six months storage and against EDTA and human serum. This radioimmunoconjugate had a biodistribution profile similar to that of (90)Y-ibritumomab, which is approved by FDA for radioimmunotherapy of NHL, and showed low brain and lung uptakes and low yttrium deposition into bone. CONCLUSION: Findings of this study suggest that further investigations may result in a lyophilized (kit) formulation of DOTA-rituximab which could be easily radiolabeled with (90)Y and (111)In in order to be used for radioimmunotherapy and radioscintigraphy of B-cell lymphoma in Iran.
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spelling pubmed-42618832014-12-10 Preparation and radiolabeling of a lyophilized (kit) formulation of DOTA-rituximab with (90)Y and (111)In for domestic radioimmunotherapy and radioscintigraphy of Non-Hodgkin’s Lymphoma Gholipour, Nazila Jalilian, Amir Reza Khalaj, Ali Johari-Daha, Fariba Yavari, Kamal Sabzevari, Omid Khanchi, Ali Reza Akhlaghi, Mehdi Daru Research Article BACKGROUND: On the basis of results of our previous investigations on (90)Y-DTPA-rituximab and in order to fulfil national demands to radioimmunoconjugates for radioscintigraphy and radioimmunotherapy of Non-Hodgkin’s Lymphoma (NHL), preparation and radiolabeling of a lyophilized formulation (kit) of DOTA-rituximab with (111)In and (90)Y was investigated. METHODS: (111)In and (90)Y with high radiochemical and radionuclide purity were prepared by (112)Cd (p,2n)(111)In nuclear reaction and a locally developed (90)Sr/(90)Y generator, respectively. DOTA-rituximab immunoconjugates were prepared by the reaction of solutions of p-SCN-Bz-DOTA and rituximab in carbonate buffer (pH = 9.5) and the number of DOTA per molecule of conjugates were determined by transchelation reaction between DOTA and arsenaso yttrium(III) complex. DOTA-rituximab immunoconjugates were labeled with (111)In and (90)Y and radioimmunoconjugates were checked for radiochemical purity by chromatography methods and for immunoreactivity by cell-binding assay using Raji cell line. The stability of radiolabeled conjugate with the approximate number of 7 DOTA molecules per one rituximab molecule which was prepared in moderate yield and showed moderate immunoreactivity, compared to two other prepared radioimmunoconjugates, was determined at different time intervals and against EDTA and human serum by chromatography methods and reducing SDS-polyacrylamide gel electrophoresis, respectively. The biodistribution of the selected radioimmunoconjugate in rats was determined by measurement of the radioactivity of different organs after sacrificing the animals by ether asphyxiation. RESULTS: The radioimmunoconjugate with approximate DOTA/rituximab molar ratio of 7 showed stability after 24 h at room temperature, after 96 h at 4°C, as the lyophilized formulation after six months storage and against EDTA and human serum. This radioimmunoconjugate had a biodistribution profile similar to that of (90)Y-ibritumomab, which is approved by FDA for radioimmunotherapy of NHL, and showed low brain and lung uptakes and low yttrium deposition into bone. CONCLUSION: Findings of this study suggest that further investigations may result in a lyophilized (kit) formulation of DOTA-rituximab which could be easily radiolabeled with (90)Y and (111)In in order to be used for radioimmunotherapy and radioscintigraphy of B-cell lymphoma in Iran. BioMed Central 2014-07-29 /pmc/articles/PMC4261883/ /pubmed/25074720 http://dx.doi.org/10.1186/2008-2231-22-58 Text en © Gholipour et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Gholipour, Nazila
Jalilian, Amir Reza
Khalaj, Ali
Johari-Daha, Fariba
Yavari, Kamal
Sabzevari, Omid
Khanchi, Ali Reza
Akhlaghi, Mehdi
Preparation and radiolabeling of a lyophilized (kit) formulation of DOTA-rituximab with (90)Y and (111)In for domestic radioimmunotherapy and radioscintigraphy of Non-Hodgkin’s Lymphoma
title Preparation and radiolabeling of a lyophilized (kit) formulation of DOTA-rituximab with (90)Y and (111)In for domestic radioimmunotherapy and radioscintigraphy of Non-Hodgkin’s Lymphoma
title_full Preparation and radiolabeling of a lyophilized (kit) formulation of DOTA-rituximab with (90)Y and (111)In for domestic radioimmunotherapy and radioscintigraphy of Non-Hodgkin’s Lymphoma
title_fullStr Preparation and radiolabeling of a lyophilized (kit) formulation of DOTA-rituximab with (90)Y and (111)In for domestic radioimmunotherapy and radioscintigraphy of Non-Hodgkin’s Lymphoma
title_full_unstemmed Preparation and radiolabeling of a lyophilized (kit) formulation of DOTA-rituximab with (90)Y and (111)In for domestic radioimmunotherapy and radioscintigraphy of Non-Hodgkin’s Lymphoma
title_short Preparation and radiolabeling of a lyophilized (kit) formulation of DOTA-rituximab with (90)Y and (111)In for domestic radioimmunotherapy and radioscintigraphy of Non-Hodgkin’s Lymphoma
title_sort preparation and radiolabeling of a lyophilized (kit) formulation of dota-rituximab with (90)y and (111)in for domestic radioimmunotherapy and radioscintigraphy of non-hodgkin’s lymphoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4261883/
https://www.ncbi.nlm.nih.gov/pubmed/25074720
http://dx.doi.org/10.1186/2008-2231-22-58
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