Radiolabeled cyclosaligenyl monophosphates of 5-iodo-2′-deoxyuridine, 5-iodo-3′-fluoro-2′,3′-dideoxyuridine, and 3′-fluorothymidine for molecular radiotherapy of cancer

Synthesis and biological evaluation

Zbigniew P. Kortylewicz, Yu Kimura, Kotaro Inoue, Elizabeth MacK, Janina Baranowska-Kortylewicz

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Targeted molecular radiotherapy opens unprecedented opportunities to eradicate cancer cells with minimal irradiation of normal tissues. Described in this study are radioactive cyclosaligenyl monophosphates designed to deliver lethal doses of radiation to cancer cells. These compounds can be radiolabeled with SPECT- and PET-compatible radionuclides as well as radionuclides suitable for Auger electron therapies. This characteristic provides an avenue for the personalized and comprehensive treatment strategy that comprises diagnostic imaging to identify sites of disease, followed by the targeted molecular radiotherapy based on the imaging results. The developed radiosynthetic methods produce no-carrier-added products with high radiochemical yield and purity. The interaction of these compounds with their target, butyrylcholinesterase, depends on the stereochemistry around the P atom. IC 50 values are in the nanomolar range. In vitro studies indicate that radiation doses delivered to the cell nucleus are sufficient to kill cells of several difficult to treat malignancies including glioblastoma and ovarian and colorectal cancers.

Original languageEnglish (US)
Pages (from-to)2649-2671
Number of pages23
JournalJournal of Medicinal Chemistry
Volume55
Issue number6
DOIs
StatePublished - Mar 22 2012

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Radiotherapy
Radioisotopes
Radiation
Butyrylcholinesterase
Neoplasms
Diagnostic Imaging
Glioblastoma
Single-Photon Emission-Computed Tomography
Cell Nucleus
Ovarian Neoplasms
Colorectal Neoplasms
Electrons
Therapeutics
alovudine
iododeoxyuridylate
In Vitro Techniques

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

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title = "Radiolabeled cyclosaligenyl monophosphates of 5-iodo-2′-deoxyuridine, 5-iodo-3′-fluoro-2′,3′-dideoxyuridine, and 3′-fluorothymidine for molecular radiotherapy of cancer: Synthesis and biological evaluation",
abstract = "Targeted molecular radiotherapy opens unprecedented opportunities to eradicate cancer cells with minimal irradiation of normal tissues. Described in this study are radioactive cyclosaligenyl monophosphates designed to deliver lethal doses of radiation to cancer cells. These compounds can be radiolabeled with SPECT- and PET-compatible radionuclides as well as radionuclides suitable for Auger electron therapies. This characteristic provides an avenue for the personalized and comprehensive treatment strategy that comprises diagnostic imaging to identify sites of disease, followed by the targeted molecular radiotherapy based on the imaging results. The developed radiosynthetic methods produce no-carrier-added products with high radiochemical yield and purity. The interaction of these compounds with their target, butyrylcholinesterase, depends on the stereochemistry around the P atom. IC 50 values are in the nanomolar range. In vitro studies indicate that radiation doses delivered to the cell nucleus are sufficient to kill cells of several difficult to treat malignancies including glioblastoma and ovarian and colorectal cancers.",
author = "Kortylewicz, {Zbigniew P.} and Yu Kimura and Kotaro Inoue and Elizabeth MacK and Janina Baranowska-Kortylewicz",
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T2 - Synthesis and biological evaluation

AU - Kortylewicz, Zbigniew P.

AU - Kimura, Yu

AU - Inoue, Kotaro

AU - MacK, Elizabeth

AU - Baranowska-Kortylewicz, Janina

PY - 2012/3/22

Y1 - 2012/3/22

N2 - Targeted molecular radiotherapy opens unprecedented opportunities to eradicate cancer cells with minimal irradiation of normal tissues. Described in this study are radioactive cyclosaligenyl monophosphates designed to deliver lethal doses of radiation to cancer cells. These compounds can be radiolabeled with SPECT- and PET-compatible radionuclides as well as radionuclides suitable for Auger electron therapies. This characteristic provides an avenue for the personalized and comprehensive treatment strategy that comprises diagnostic imaging to identify sites of disease, followed by the targeted molecular radiotherapy based on the imaging results. The developed radiosynthetic methods produce no-carrier-added products with high radiochemical yield and purity. The interaction of these compounds with their target, butyrylcholinesterase, depends on the stereochemistry around the P atom. IC 50 values are in the nanomolar range. In vitro studies indicate that radiation doses delivered to the cell nucleus are sufficient to kill cells of several difficult to treat malignancies including glioblastoma and ovarian and colorectal cancers.

AB - Targeted molecular radiotherapy opens unprecedented opportunities to eradicate cancer cells with minimal irradiation of normal tissues. Described in this study are radioactive cyclosaligenyl monophosphates designed to deliver lethal doses of radiation to cancer cells. These compounds can be radiolabeled with SPECT- and PET-compatible radionuclides as well as radionuclides suitable for Auger electron therapies. This characteristic provides an avenue for the personalized and comprehensive treatment strategy that comprises diagnostic imaging to identify sites of disease, followed by the targeted molecular radiotherapy based on the imaging results. The developed radiosynthetic methods produce no-carrier-added products with high radiochemical yield and purity. The interaction of these compounds with their target, butyrylcholinesterase, depends on the stereochemistry around the P atom. IC 50 values are in the nanomolar range. In vitro studies indicate that radiation doses delivered to the cell nucleus are sufficient to kill cells of several difficult to treat malignancies including glioblastoma and ovarian and colorectal cancers.

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