SN-38 (7-ethyl-10-hydroxy camptothecin) is a topoisomerase I inhibitor that is the active chemotherapeutic agent of irinotecan, indicated for colon cancer. Because the rate of response to irinotecan treatment is low, it is of interest to have a prognostic indicator to identify and more selectively treat those who are likely to respond to treatment. We have therefore prepared SN-38 labeled with carbon-11. SN-38 was prepared by radical oxidation of 3-[11C]propionaldehyde and subsequent radical addition of the ethyl fragment to 10-hydroxycamptothecin. Labeled propionaldehyde was prepared by reaction of methyl iodide with 2-lithiomethyl-1,3-dioxolane. Overall chemical yield was 34% from carbon dioxide. The murine biodistribution and radiation dosimetry of [11C]SN-38 was measured by PET scanning in preparation for initial human studies. Biodistribution was fairly uniform except for hepatobiliary and urinary excretion. Copyright © 2010 John Wiley & Sons, Ltd.