Diesterified derivatives of 5-iodo-2'-deoxyuridine as cerebral tumor tracers.

With the aim to develop beneficial tracers for cerebral tumors, we tested two novel 5-iodo-2'-deoxyuridine (IUdR) derivatives, diesterified at the deoxyribose residue. The substances were designed to enhance the uptake into brain tumor tissue and to prolong the availability in the organism. We...

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Autores principales:	Thomas W Rösler, Andreas Matusch, Damiano Librizzi, Oscar Arias-Carrión, Nils Freundlieb, Helmut Hoeffken, Wolfgang H Oertel, Candan Depboylu, Günter U Höglinger
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6b5898f7f8b64014bc6b4d20e7885902
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spelling	oai:doaj.org-article:6b5898f7f8b64014bc6b4d20e78859022021-11-25T06:08:22ZDiesterified derivatives of 5-iodo-2'-deoxyuridine as cerebral tumor tracers.1932-620310.1371/journal.pone.0102397https://doaj.org/article/6b5898f7f8b64014bc6b4d20e78859022014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25028935/?tool=EBIhttps://doaj.org/toc/1932-6203With the aim to develop beneficial tracers for cerebral tumors, we tested two novel 5-iodo-2'-deoxyuridine (IUdR) derivatives, diesterified at the deoxyribose residue. The substances were designed to enhance the uptake into brain tumor tissue and to prolong the availability in the organism. We synthesized carrier added 5-[125I]iodo-3',5'-di-O-acetyl-2'-deoxyuridine (Ac2[125I]IUdR), 5-[125I]iodo-3',5'-di-O-pivaloyl-2'-deoxyuridine (Piv2[125I]IUdR) and their respective precursor molecules for the first time. HPLC was used for purification and to determine the specific activities. The iodonucleoside tracer were tested for their stability against human thymidine phosphorylase. DNA integration of each tracer was determined in 2 glioma cell lines (Gl261, CRL2397) and in PC12 cells in vitro. In mice, we measured the relative biodistribution and the tracer uptake in grafted brain tumors. Ac2[125I]IUdR, Piv2[125I]IUdR and [125I]IUdR (control) were prepared with labeling yields of 31-47% and radiochemical purities of >99% (HPLC). Both diesterified iodonucleoside tracers showed a nearly 100% resistance against degradation by thymidine phosphorylase. Ac2[125I]IUdR and Piv2[125I]IUdR were specifically integrated into the DNA of all tested tumor cell lines but to a less extend than the control [125I]IUdR. In mice, 24 h after i.p. injection, brain radioactivity uptakes were in the following order Piv2[125I]IUdR>Ac2[125I]IUdR>[125I]IUdR. For Ac2[125I]IUdR we detected lower amounts of radioactivities in the thyroid and stomach, suggesting a higher stability toward deiodination. In mice bearing unilateral graft-induced brain tumors, the uptake ratios of tumor-bearing to healthy hemisphere were 51, 68 and 6 for [125I]IUdR, Ac2[125I]IUdR and Piv2[125I]IUdR, respectively. Esterifications of both deoxyribosyl hydroxyl groups of the tumor tracer IUdR lead to advantageous properties regarding uptake into brain tumor tissue and metabolic stability.Thomas W RöslerAndreas MatuschDamiano LibrizziOscar Arias-CarriónNils FreundliebHelmut HoeffkenWolfgang H OertelCandan DepboyluGünter U HöglingerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 7, p e102397 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Thomas W Rösler Andreas Matusch Damiano Librizzi Oscar Arias-Carrión Nils Freundlieb Helmut Hoeffken Wolfgang H Oertel Candan Depboylu Günter U Höglinger Diesterified derivatives of 5-iodo-2'-deoxyuridine as cerebral tumor tracers.
description	With the aim to develop beneficial tracers for cerebral tumors, we tested two novel 5-iodo-2'-deoxyuridine (IUdR) derivatives, diesterified at the deoxyribose residue. The substances were designed to enhance the uptake into brain tumor tissue and to prolong the availability in the organism. We synthesized carrier added 5-[125I]iodo-3',5'-di-O-acetyl-2'-deoxyuridine (Ac2[125I]IUdR), 5-[125I]iodo-3',5'-di-O-pivaloyl-2'-deoxyuridine (Piv2[125I]IUdR) and their respective precursor molecules for the first time. HPLC was used for purification and to determine the specific activities. The iodonucleoside tracer were tested for their stability against human thymidine phosphorylase. DNA integration of each tracer was determined in 2 glioma cell lines (Gl261, CRL2397) and in PC12 cells in vitro. In mice, we measured the relative biodistribution and the tracer uptake in grafted brain tumors. Ac2[125I]IUdR, Piv2[125I]IUdR and [125I]IUdR (control) were prepared with labeling yields of 31-47% and radiochemical purities of >99% (HPLC). Both diesterified iodonucleoside tracers showed a nearly 100% resistance against degradation by thymidine phosphorylase. Ac2[125I]IUdR and Piv2[125I]IUdR were specifically integrated into the DNA of all tested tumor cell lines but to a less extend than the control [125I]IUdR. In mice, 24 h after i.p. injection, brain radioactivity uptakes were in the following order Piv2[125I]IUdR>Ac2[125I]IUdR>[125I]IUdR. For Ac2[125I]IUdR we detected lower amounts of radioactivities in the thyroid and stomach, suggesting a higher stability toward deiodination. In mice bearing unilateral graft-induced brain tumors, the uptake ratios of tumor-bearing to healthy hemisphere were 51, 68 and 6 for [125I]IUdR, Ac2[125I]IUdR and Piv2[125I]IUdR, respectively. Esterifications of both deoxyribosyl hydroxyl groups of the tumor tracer IUdR lead to advantageous properties regarding uptake into brain tumor tissue and metabolic stability.
format	article
author	Thomas W Rösler Andreas Matusch Damiano Librizzi Oscar Arias-Carrión Nils Freundlieb Helmut Hoeffken Wolfgang H Oertel Candan Depboylu Günter U Höglinger
author_facet	Thomas W Rösler Andreas Matusch Damiano Librizzi Oscar Arias-Carrión Nils Freundlieb Helmut Hoeffken Wolfgang H Oertel Candan Depboylu Günter U Höglinger
author_sort	Thomas W Rösler
title	Diesterified derivatives of 5-iodo-2'-deoxyuridine as cerebral tumor tracers.
title_short	Diesterified derivatives of 5-iodo-2'-deoxyuridine as cerebral tumor tracers.
title_full	Diesterified derivatives of 5-iodo-2'-deoxyuridine as cerebral tumor tracers.
title_fullStr	Diesterified derivatives of 5-iodo-2'-deoxyuridine as cerebral tumor tracers.
title_full_unstemmed	Diesterified derivatives of 5-iodo-2'-deoxyuridine as cerebral tumor tracers.
title_sort	diesterified derivatives of 5-iodo-2'-deoxyuridine as cerebral tumor tracers.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/6b5898f7f8b64014bc6b4d20e7885902
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Diesterified derivatives of 5-iodo-2'-deoxyuridine as cerebral tumor tracers.

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