1209526-88-4Relevant academic research and scientific papers
Norepinephrine-Transporter-Targeted and DNA-Co-Targeted Theranostic Guanidines
Kortylewicz, Zbigniew P.,Coulter, Donald W.,Han, Guang,Baranowska-Kortylewicz, Janina
supporting information, p. 2051 - 2073 (2020/03/31)
High risk neuroblastoma often recurs, even with aggressive treatments. Clinical evidence suggests that proliferative activities are predictive of poor outcomes. This report describes syntheses, characterization, and biological properties of theranostic guanidines that target norepinephrine transporter and undergo intracellular processing, and subsequently their catabolites are efficiently incorporated into DNA of proliferating neuroblastoma cells. Radioactive guanidines are synthesized from 5-radioiodo-2′-deoxyuridine, a molecular radiotherapy platform with clinically proven minimal toxicities and DNA-targeting properties. The transport of radioactive guanidines into neuroblastoma cells is active as indicated by the competitive suppression of cellular uptake by meta-iodobenzylguanidine. The rate of intracellular processing and DNA uptake is influenced by the agent's catabolic stability and cell population doubling times. The radiotoxicity is directly proportional to DNA uptake and duration of exposure. Biodistribution of 5-[125I]iodo-3′-O-(?-guanidinohexanoyl)-2′-deoxyuridine in a mouse neuroblastoma model shows significant tumor retention of radioactivity. Neuroblastoma xenografts regress in response to the clinically achievable doses of this agent.
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
Kortylewicz, Zbigniew P.,Kimura, Yu,Inoue, Kotaro,MacK, Elizabeth,Baranowska-Kortylewicz, Janina
scheme or table, p. 2649 - 2671 (2012/06/16)
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. IC50 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.
Radiolabeled 5-iodo-3′-O-(17β-succinyl-5α-androstan-3-one) -2′-deoxyuridine and its 5′-monophosphate for imaging and therapy of androgen receptor-positive cancers: Synthesis and biological evaluation
Kortylewicz, Zbigniew P.,Nearman, Jessica,Baranowska-Kortylewicz, Janina
experimental part, p. 5124 - 5143 (2010/04/02)
High levels of androgen receptor (AR) are often indicative of recurrent, advanced, or metastatic cancers. These conditions are also characterized by a high proliferative fraction. 5-Radioiodo-3′-O-(17β-succinyl-5α- androstan-3-one)-2′-deoxyuridine 8 and 5
