Cargando…

DNA damage in blood lymphocytes in patients after (177)Lu peptide receptor radionuclide therapy

PURPOSE: The aim of the study was to investigate DNA double strand break (DSB) formation and its correlation with the absorbed dose to the blood lymphocytes of patients undergoing their first peptide receptor radionuclide therapy (PRRT) with (177)Lu-labelled DOTATATE/DOTATOC. METHODS: The study grou...

Descripción completa

Detalles Bibliográficos
Autores principales: Eberlein, Uta, Nowak, Carina, Bluemel, Christina, Buck, Andreas Konrad, Werner, Rudolf Alexander, Scherthan, Harry, Lassmann, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4554740/
https://www.ncbi.nlm.nih.gov/pubmed/26048612
http://dx.doi.org/10.1007/s00259-015-3083-9
_version_ 1782388082907021312
author Eberlein, Uta
Nowak, Carina
Bluemel, Christina
Buck, Andreas Konrad
Werner, Rudolf Alexander
Scherthan, Harry
Lassmann, Michael
author_facet Eberlein, Uta
Nowak, Carina
Bluemel, Christina
Buck, Andreas Konrad
Werner, Rudolf Alexander
Scherthan, Harry
Lassmann, Michael
author_sort Eberlein, Uta
collection PubMed
description PURPOSE: The aim of the study was to investigate DNA double strand break (DSB) formation and its correlation with the absorbed dose to the blood lymphocytes of patients undergoing their first peptide receptor radionuclide therapy (PRRT) with (177)Lu-labelled DOTATATE/DOTATOC. METHODS: The study group comprised 16 patients receiving their first PRRT. At least six peripheral blood samples were obtained before, and between 0.5 h and 48 h after radionuclide administration. From the time–activity curves of the blood and the whole body, residence times for blood self-irradiation and whole-body irradiation were determined. Peripheral blood lymphocytes were isolated, fixed with ethanol and subjected to immunofluorescence staining for colocalizing γ-H2AX/53BP1 DSB-marking foci. The average number of DSB foci per cell per patient sample was determined as a function of the absorbed dose to the blood and compared with an in vitro calibration curve established in our laboratory with (131)I and (177)Lu. RESULTS: The average number of radiation-induced foci (RIF) per cell increased over the first 5 h after radionuclide administration and decreased thereafter. A linear fit from 0 to 5 h as a function of the absorbed dose to the blood agreed with our in vitro calibration curve. At later time-points the number of RIF decreased, indicating progression of DNA repair. CONCLUSION: Measurements of RIF and the absorbed dose to the blood after systemic administration of (177)Lu may be used to obtain data on the individual dose–response relationships in vivo. Individual patient data were characterized by a linear dose-dependent increase and an exponential decay function describing repair. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00259-015-3083-9) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-4554740
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Springer Berlin Heidelberg
record_format MEDLINE/PubMed
spelling pubmed-45547402015-09-04 DNA damage in blood lymphocytes in patients after (177)Lu peptide receptor radionuclide therapy Eberlein, Uta Nowak, Carina Bluemel, Christina Buck, Andreas Konrad Werner, Rudolf Alexander Scherthan, Harry Lassmann, Michael Eur J Nucl Med Mol Imaging Original Article PURPOSE: The aim of the study was to investigate DNA double strand break (DSB) formation and its correlation with the absorbed dose to the blood lymphocytes of patients undergoing their first peptide receptor radionuclide therapy (PRRT) with (177)Lu-labelled DOTATATE/DOTATOC. METHODS: The study group comprised 16 patients receiving their first PRRT. At least six peripheral blood samples were obtained before, and between 0.5 h and 48 h after radionuclide administration. From the time–activity curves of the blood and the whole body, residence times for blood self-irradiation and whole-body irradiation were determined. Peripheral blood lymphocytes were isolated, fixed with ethanol and subjected to immunofluorescence staining for colocalizing γ-H2AX/53BP1 DSB-marking foci. The average number of DSB foci per cell per patient sample was determined as a function of the absorbed dose to the blood and compared with an in vitro calibration curve established in our laboratory with (131)I and (177)Lu. RESULTS: The average number of radiation-induced foci (RIF) per cell increased over the first 5 h after radionuclide administration and decreased thereafter. A linear fit from 0 to 5 h as a function of the absorbed dose to the blood agreed with our in vitro calibration curve. At later time-points the number of RIF decreased, indicating progression of DNA repair. CONCLUSION: Measurements of RIF and the absorbed dose to the blood after systemic administration of (177)Lu may be used to obtain data on the individual dose–response relationships in vivo. Individual patient data were characterized by a linear dose-dependent increase and an exponential decay function describing repair. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00259-015-3083-9) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2015-06-06 2015 /pmc/articles/PMC4554740/ /pubmed/26048612 http://dx.doi.org/10.1007/s00259-015-3083-9 Text en © The Author(s) 2015 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Eberlein, Uta
Nowak, Carina
Bluemel, Christina
Buck, Andreas Konrad
Werner, Rudolf Alexander
Scherthan, Harry
Lassmann, Michael
DNA damage in blood lymphocytes in patients after (177)Lu peptide receptor radionuclide therapy
title DNA damage in blood lymphocytes in patients after (177)Lu peptide receptor radionuclide therapy
title_full DNA damage in blood lymphocytes in patients after (177)Lu peptide receptor radionuclide therapy
title_fullStr DNA damage in blood lymphocytes in patients after (177)Lu peptide receptor radionuclide therapy
title_full_unstemmed DNA damage in blood lymphocytes in patients after (177)Lu peptide receptor radionuclide therapy
title_short DNA damage in blood lymphocytes in patients after (177)Lu peptide receptor radionuclide therapy
title_sort dna damage in blood lymphocytes in patients after (177)lu peptide receptor radionuclide therapy
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4554740/
https://www.ncbi.nlm.nih.gov/pubmed/26048612
http://dx.doi.org/10.1007/s00259-015-3083-9
work_keys_str_mv AT eberleinuta dnadamageinbloodlymphocytesinpatientsafter177lupeptidereceptorradionuclidetherapy
AT nowakcarina dnadamageinbloodlymphocytesinpatientsafter177lupeptidereceptorradionuclidetherapy
AT bluemelchristina dnadamageinbloodlymphocytesinpatientsafter177lupeptidereceptorradionuclidetherapy
AT buckandreaskonrad dnadamageinbloodlymphocytesinpatientsafter177lupeptidereceptorradionuclidetherapy
AT wernerrudolfalexander dnadamageinbloodlymphocytesinpatientsafter177lupeptidereceptorradionuclidetherapy
AT scherthanharry dnadamageinbloodlymphocytesinpatientsafter177lupeptidereceptorradionuclidetherapy
AT lassmannmichael dnadamageinbloodlymphocytesinpatientsafter177lupeptidereceptorradionuclidetherapy