Synthesis and biologic evaluation of a radioiodinated quinazolinone derivative for enzyme-mediated insolubilization therapy
| Autor: | Amin I. Kassis, S. James Adelstein, Ravi S. Harapanhalli, Bassam A. Dahman, Nan-hui Ho, Ketai Wang, Kai Chen |
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| Rok vydání: | 2002 |
| Předmět: |
Biodistribution
Biomedical Engineering Pharmaceutical Science Bioengineering Sensitivity and Specificity Fluorescence Iodine Radioisotopes chemistry.chemical_compound Mice Drug Delivery Systems In vivo Animals Prodrugs Quinazolinone Quinazolinones Pharmacology chemistry.chemical_classification Chemistry Organic Chemistry Prodrug Alkaline Phosphatase In vitro Quaternary Ammonium Compounds Enzyme Biochemistry Solubility Organ Specificity Quinazolines Alkaline phosphatase Derivative (chemistry) Biotechnology |
| Zdroj: | Bioconjugate chemistry. 13(2) |
| ISSN: | 1043-1802 |
| Popis: | We have developed a new strategy that aims to concentrate therapeutic radionuclides within solid tumors. This approach, which we have named EMIT (enzyme-mediated insolubilization therapy), is a method for enzyme-dependent, site-specific, in vivo precipitation of a radioactive molecule (from a water-soluble precursor) within the extracellular space of solid tumors. The prodrug, ammonium 2-(2'-phosphoryloxyphenyl)-6-iodo-4-(3H)-quinazolinone, labeled with iodine-125 ((125)IPD) and its authentic compound labeled with iodine-127 (IPD) have been synthesized, purified, and characterized. The alkaline phosphatase (ALP)-mediated conversion of these water-soluble nonfluorescent prodrugs to the water-insoluble fluorescent species, iodine-125-labeled 2-(2'-hydroxyphenyl)-6-iodo-4-(3H)-quinazolinone ((125)ID) and its iodine-127-labeled derivative (ID), has been demonstrated in vitro. Biodistribution studies in mice indicate that both (125)IPD and (125)ID are minimally retained by most tissues and organs. In addition, following its intravenous injection in mice, (125)IPD is localized in ALP-rich regions and converted to (125)ID, which remains indefinitely within the tissues where it is produced. We believe that EMIT is a strategy that will lead to the active and specific concentration and entrapment of therapeutic radionuclides within solid tumors, the consequent protracted irradiation of tumor cells within the range of the emitted particles, and the effective therapy of solid tumors. |
| Databáze: | OpenAIRE |
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