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

G. Mariani, S. Di Sacco, R. Bonini, L. Di Luca, S. Buralli, D. Bonora, S. Ricci, Janina Baranowska-Kortylewicz, S. J. Adelstein, A. Falcone, A. I. Kassis

Research output: Contribution to journalArticle

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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 - Jan 1 1996

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Idoxuridine
Deoxyuridine
Leucovorin
Fluorouracil
Colorectal Neoplasms
Neoplasm Metastasis
Liver
Neoplasms
Thymidylate Synthase
Hepatic Artery
Drug Combinations
Diagnostic Imaging
Thymidine
Electrons

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

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. / Mariani, G.; Di Sacco, S.; Bonini, R.; Di Luca, L.; Buralli, S.; Bonora, D.; Ricci, S.; Baranowska-Kortylewicz, Janina; Adelstein, S. J.; Falcone, A.; Kassis, A. I.

In: Acta Oncologica, Vol. 35, No. 7, 01.01.1996, p. 941-945.

Research output: Contribution to journalArticle

Mariani, G. ; Di Sacco, S. ; Bonini, R. ; Di Luca, L. ; Buralli, S. ; Bonora, D. ; Ricci, S. ; Baranowska-Kortylewicz, Janina ; Adelstein, S. J. ; Falcone, A. ; Kassis, A. I. / 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: Acta Oncologica. 1996 ; Vol. 35, No. 7. pp. 941-945.
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AU - Mariani, G.

AU - Di Sacco, S.

AU - Bonini, R.

AU - Di Luca, L.

AU - Buralli, S.

AU - Bonora, D.

AU - Ricci, S.

AU - Baranowska-Kortylewicz, Janina

AU - Adelstein, S. J.

AU - Falcone, A.

AU - Kassis, A. I.

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