In Vivo and in Vitro MR Biomarkers for Choline Kinase Inhibition in Human Colon Cancer HCT-116

Moses Darpolor¹, Peter Kennealey², H. Carl Le¹, Kristen Zakian¹, Ellen Ackerstaff¹, Asif Rizwan¹, Jin-Hong Chen², Eliot Sambol², Gary Schwartz³, Samuel Singer², Jason Koutcher^1,3

Combined irinotecan and flavopiridol therapy is in clinical trials to treat human colon malignancies. Using in vivo and in vitro MR measurements we report here several critical HCT-116 cellular markers from the treatment. We have shown that flavopiridol is effective in inhibiting choline kinase by lowering phosphocholine/choline levels in vitro, while 31P MRSI detected an in vivo transient decrease in phosophocholine level following the treatment with both drugs. Detectable cholesterol/CH3 levels were observed to increase in tandem with HCT-116 cancer cell apoptotic fraction.