Pilot clinical trial of 5-[125I]iodo-2'-deoxyuridine in the treatment of colorectal cancer metastatic to the liver.
The thymidine analog, 5-iodo-2'-deoxyuridine (IUdR), is incorporated in the DNA of cells in the S phase. When incorporated into DNA, short-range Auger electrons emitted by 125I-labeled IUdR can cause double-strand breaks, delivering a lethal radiation dose to the cell. We conducted therapeutic trial to evaluate[125I/131I]IUdR pharmacokinetics in liver metastases from colorectal cancer. Dosimetry, safety, and therapeutic potential were assessed.


METHODS
Four patients were each infused with 5 mCi [125I]IUdR and 10 mCi [131I]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.


RESULTS
All patients had [125I]IUdR and [131I]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 actively dividing normal tissues. Radioactivity in all tumor DNA samples was greater than background, while that in normal liver cell DNA was at background levels. 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.


CONCLUSIONS
There is persistent uptake of [125I]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.
Macapinlac
H A
HA
Department of Radiology, Memorial Sloan-Kettering Cancer Center, Memorial Hospital, New York, NY 10021, USA.
Kemeny
N
N
Daghighian
F
F
Finn
R
R
Zhang
J
J
Humm
J
J
Squire
O
O
Larson
S M
SM
D000328:Adult; D000368:Aged; D002851:Chromatography, High Pressure Liquid; D015179:Colorectal Neoplasms / Q000473:pathology*; D006499:Hepatic Artery; D006801:Humans; D007065:Idoxuridine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007261:Infusions, Intra-Arterial; D007457:Iodine Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy* / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011859:Radiography; D011877:Radionuclide Imaging; D011879:Radiotherapy Dosage; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D007065:Idoxuridine