Pharmacokinetics and dosimetry of iodine-125-IUdR in the treatment of colorectal cancer metastatic to liver.

ABSTRACT

UNLABELLED The radiotoxicity of 125I is highly sensitive to the site of decay relative to nuclear DNA. This paper describes a new approach, based upon pharmacokinetic clearance of radioactivity from the tumor, with which to quantify the fraction of [125I]IUdR incorporated within the DNA of tumor cells. METHODS: Patients were injected with [125I]IUdR through the hepatic artery. Iodine-131-IUdR was used as a tracer for imaging and quantitation. Both conventional and DNA-level dosimetry were performed. RESULTS: We calculated that if 15% of the tumor cells were in S phase at the time of injection, there would be 250 decays of 125I in the DNA per tumor cell after an infusion of 5 mCi [125I]IUdR. According to in vitro data based on 5 x 10(8) cells per g tumor, 99% of these cells in S phase would be killed. CONCLUSION: The estimate of cell inactivation is strongly dependent on the number of cells per gram and the fraction of cells in S phase at the time of injection, which indicates that repeat injections would be necessary to achieve a therapeutic effect.