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

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

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14 Scopus citations

Abstract

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 I-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.

Original languageEnglish (US)
Pages (from-to)941-945
Number of pages5
JournalActa Oncologica
Volume35
Issue number7
DOIs
StatePublished - 1996

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Radiology Nuclear Medicine and imaging

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