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Biochemical Modulation by 5-Fluorouracil and 1-Folinic Acid of Tumor Uptake of Intra-Arterial 5-[ 123 I]Iodo-2'-Deoxyuridine in Patients with Liver Metastases from Colorectal Cancer

1996; Taylor & Francis; Volume: 35; Issue: 7 Linguagem: Inglês

10.3109/02841869609104049

1651-226X

Giuliano Mariani, Sonia Di Sacco, R. Bonini, Lorella Di Luca, Simona Buralli, Danilo Bonora, Sergio Ricci, Janina Baranowska‐Kortylewicz, S. James Adelstein, Alfredo Falcone, Amin I. Kassis,

Hepatocellular Carcinoma Treatment and Prognosis

AbstractIn 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.