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dc.contributor.authorPospisil, Pavel
dc.contributor.authorWang, Ketai
dc.contributor.authorAl Aowad, Ayman F.
dc.contributor.authorIyer, Lakshmanan K.
dc.contributor.authorAdelstein, Stanley
dc.contributor.authorKassis, Amin I.
dc.date.accessioned2019-08-19T09:42:14Z
dc.date.issued2007-03-01
dc.identifier.citationPospisil, Pavel, Ketai Wang, Ayman F. Al Aowad, Lakshmanan K. Iyer, S. James Adelstein, and Amin I. Kassis. 2007. “Computational Modeling and Experimental Evaluation of a Novel Prodrug for Targeting the Extracellular Space of Prostate Tumors.” Cancer Research 67 (5): 2197–2205. https://doi.org/10.1158/0008-5472.can-06-3309.en_US
dc.identifier.issn0008-5472en_US
dc.identifier.issn1538-7445en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41200907*
dc.description.abstractWe are developing a noninvasive approach for targeting imaging and therapeutic radionuclides to prostate cancer. Our method, Enzyme-Mediated Cancer Imaging and Therapy (EMCIT), aims to use enzyme-dependent, site-specific, in vivo precipitation of a radioactive molecule within the extracellular space of solid tumors. Advanced methods for data mining of the literature, protein databases, and knowledge bases (IT.Omics LSGraph and Ingenuity Systems) identified prostatic acid phosphatase (PAP) as an enzyme overexpressed in prostate cancer and secreted in the extracellular space. Using AutoDock 3.0 software, the prodrug ammonium 2-(2'-phosphoryloxyphenyl)-6-iodo-4-(3H)-quinazolinone (IQ(2-P)) was docked in silico into the X-ray structure of PAP. The data indicate that IQ(2-P) docked into the PAP active site with a calculated inhibition constant (K-i) more favorable than that of the PAP inhibitor alpha-benzylaminobenzylphosphonic acid. When (125)IQ(2-P), the radioiodinated form of the water-soluble prodrug, was incubated with PAP, rapid hydrolysis of the compound was observed as exemplified by formation of the water-insoluble 2-(2'-hydroxyphenyl)-6-[I-125] iodo-4-(3H)-quinazolinone ((125)IQ(2-OH))- Similarly, the incubation of IQ(2-P) with human LNCaP, PC-3, and 22110 prostate tumor cells resulted in the formation of large fluorescent IQ(2-OH) crystals. No hydrolysis was seen in the presence of normal human cells. Autoradiography of tumor cells incubated with (125)IQ(2-P) showed accumulation of radioactive grains ((125)IQ(2-OH)) around the cells. We anticipate that the EMCIT approach will enable the active in vivo entrapment of radioimaging and radio-therapeutic compounds within the extracellular spaces of primary prostate tumors and their metastases.en_US
dc.language.isoen_USen_US
dc.publisherAmerican Association for Cancer Research (AACR)en_US
dash.licenseMETA_ONLY
dc.subjectCancer Researchen_US
dc.subjectOncologyen_US
dc.titleComputational Modeling and Experimental Evaluation of a Novel Prodrug for Targeting the Extracellular Space of Prostate Tumorsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalCancer Researchen_US
dash.depositing.authorAdelstein, Stanley
dc.date.available2019-08-19T09:42:14Z
dash.workflow.comments1Science Serial ID 19342en_US
dc.identifier.doi10.1158/0008-5472.can-06-3309
dc.source.journalCancer Res
dash.source.volume67;5
dash.source.page2197-2205
dash.contributor.affiliatedAdelstein, Stanley


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