Pilot clinical trial of 5-[{sup 125}I] iodo-2{prime}-deoxyuridine in the treatment of colorectal cancer metastic to the liver
- Memorial Sloan-Kettering Cancer Center, New York, NY (United States); and others
The thymidine analog, 5-iodo-2{prime}-deoxyuridine (IUdR), is incorporated in the DNA of cell sin the S phase. When incorporated in the DNA, short-range Auger electrons emitted by {sup 125}I-labeled IUdR can cause double-strand breaks, delivering a lethal radiation dose to the cell. We conducted therapeutic trial to evaluate [{sup 125}I/{sup 131}I]IUdR pharmacokinetics in liver metastases from colorectal cancer. Dosimetry, safety, and therapeutic potential were assessed. Four patients were each infused with 5 mCi [{sup 125}I]IUdR and 10 mCi [{sup 131}I]IUdR through the sideport of a hepatic artery pump. Iodine-131 images were quantitated and used for pharmacokinetic studies. The radioactivity in the DNA of biopsy samples of tumor, normal liver and bone marrow, obtained 24 or 48 hr after injection, was counted. All patients had [{sup 125}I]IUdR and [{sup 131}I]IUdR uptake in tumor, with a biexponential clearance. Repeat injections in individual patients showed little variation in tumor uptake, especially in the slow clearance component. On planar images, no long-term retention was seen in bone marrow or other activity dividing normal tissues. Radioactivity in the DNA of one marrow sample taken at 24 hr was above background, but in another taken at 48 hr it was equal to background levels. No side effects were noted, no hematologic toxicity was observed in any patients and no tumor responses were seen. There is persisten uptake of [{sup 125}I]IUdR in hepatic tumors, thereby making hepatic artery infusion a suitable mode of delivery for therapy. Repeat injections will be needed because only 15%-50% of tumor cells are in the S phase. Based on results from this pilot study, a therapeutic regimen is being planned. 43 refs. 2 figs.
- DOE Contract Number:
- FG02-86ER60407
- OSTI ID:
- 381022
- Journal Information:
- Journal of Nuclear Medicine, Vol. 37, Issue Suppl.4; Other Information: PBD: Apr 1996
- Country of Publication:
- United States
- Language:
- English
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