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Lee, Seung Jin; Kang, Hye Young; Kim, Seog Young; Chung, Jin Hwa; Oh, Seung Jun; Ryu, Jin-Sook; Kim, Sung-Bae; Kang, Jong Soon; Park, Song-Kyu; Kim, Hwan Mook; Kim, Myung-Hwa; Moon, Dae Hyuk
European journal of nuclear medicine and molecular imaging, 08/2011, Letnik: 38, Številka: 8Journal Article
Purpose: We determined whether super(18)Ffluorothymidine (FLT) positron emission tomography (PET) can detect early effects on tumor proliferation of JAC106, a new anti-tubulin agent. Methods: Inhibition of tubulin polymerization and super(3)Hcolchicine binding were assessed in vitro. The effects of JAC106 on cytotoxicity, mitotic arrest, super(18)FFLT uptake, and thymidine kinase 1 (TK1) activity were examined in SW620 and KB-V1 cells. Dose-dependent antitumor effects of JAC106 were monitored by measuring tumor growth and by dynamic super(18)FFLT PET imaging in mice bearing SW620 and KB-V1 tumors. The proliferation status of tumors was examined. Results: JAC106 potently inhibited tubulin polymerization and decreased the viability of SW620 (p<0.001, half maximal inhibitory concentration, IC sub(50)=3.15+/-1.4) and KB-V1 (p<0.01, IC sub(50)=21.84+/-24.59) cells. Exposure to JAC106 induced mitotic arrest starting at 18 h and dose-dependently increased super(18)FFLT uptake/110 super(5) cells (p<0.05) and TK1 activity and expression in vitro. Administration of 30 mg/kg JAC106 to mice inhibited the growth of SW620 and KB-VI tumors (%T/C 3.34 and 20.6%, respectively). The baseline standardized uptake values (SUV) of SW620 and KB-V1 tumors were 0.96+/-0.31 and 2.29+/-0.70, respectively, with a significant difference (p<0.01). After 3 days of treatment with 30 mg/kg JAC106, the super(18)FFLT SUVs of SW620 and KB-V1 tumors, normalized to those before treatment, were 77.9+/-22.4% (p=0.059) and 43.2+/-14.0% (p<0.01), respectively. JAC106 significantly decreased the number of Ki-67-positive cells, TK1 activity, cell fraction in G sub(0)G sub(1) phase, and tumor expression of cyclins E, A, and B1 on day 3. Conclusion: super(18)FFLT PET can be used to monitor JAC106 inhibition of tumor growth, beginning 3 days after treatment. Incorporation of super(18)FFLT PET may be useful in the early clinical development of JAC106.
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Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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