Biochemical modulation by 5-fluorouracil and 1-folinic acid of tumor uptake of intra-arterial 5-[123I]iodo-2'deoxyuridine in patients with liver metastases from colorectal cancer.
In previous studies we demonstrated a high tumor-targeting value of the 123I-labeled thymidine analogue 5-iodo-2'-deoxyuridine (IUdR) infused intra-arterially in patients with liver metastases from colorectal cancer. In the present study we have explored the possibility of enhancing tumor uptake of [123I]IUdR, by biochemical modulation with 5-fluorouracil (5-FU) and 1-folinic acid (FA), a drug combination known to inhibit thymidylate synthetase in tumor cells. The investigation was carried out employing diagnostic imaging doses of [123I]IUdR, much lower than possible therapeutic levels. In the baseline study, [123I]IUdR was infused into the hepatic artery of patients with inoperable liver metastases from colorectal cancer, and a second infusion was performed one week later, after intra-arterial administration of 5-FU and FA. The effect was evaluated by comparing tumor uptake of [123I]IUdR in the second study with that of the baseline study. The average tumor uptake immediately after [123I]IUdR infusion was 9.1% ID in the baseline study, increasing to 14.9% ID after pretreatment with 5-FU and FA. The average enhancement in early tumor uptake of [123I]IUdR induced by biochemical modulation was 72%. This enhancement was sustained at 18 and 42 hours after infusion (stable uptake). The results encourage the pretreatment of patients with 5-FU and FA prior to radioiodinated IUdR administration and suggest its inclusion in therapeutic protocols employing IUdR labeled with 123I or 125I as a source of highly cytotoxic Auger electrons.
Mariani
G
G
Nuclear Medicine Service, Department of Internal Medicine, University of Genoa, Italy. dimi@unige.it
Di Sacco
S
S
Bonini
R
R
Di Luca
L
L
Buralli
S
S
Bonora
D
D
Ricci
S
S
Baranowska-Kortylewicz
J
J
Adelstein
S J
SJ
Falcone
A
A
Kassis
A I
AI
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D015179:Colorectal Neoplasms; D005240:Feasibility Studies; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D007065:Idoxuridine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007261:Infusions, Intra-Arterial; D007457:Iodine Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002955:Leucovorin / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000532:radiotherapy / Q000556:secondary*; D008297:Male; D008875:Middle Aged
D000964:Antimetabolites, Antineoplastic; D007457:Iodine Radioisotopes; D007065:Idoxuridine; D002955:Leucovorin; D005472:Fluorouracil