We previously showed the tumor-targeting potential of the 125I-labeled thymidine analog 5-iodo-2′-deoxyuridine (IUdR) injected intratumorally in patients with high tumor-cell kinetics. In this study, we evaluated the tumor incorporation of [ 123I]IUdR infused intra-arterially in patients with liver metastases from colorectal cancer. Methods: Iodine-123-IUdR (110-300 MBq, 3-8 mCi, specific activity, 150-200 Ci/μmole) was infused into the hepatic artery of 16 patients with inoperable liver metastases over 30-45 min through a permanent intra-arterial catheter. A dynamic sequence during infusion, spot images, whole-body scans and SPECT acquisitions were recorded up to 42 hr. Blood and urine samples were obtained for biodistribution and HPLC analyses. Results: In the 14 patients with adequate tumor perfusion patterns, tumor uptake reached 2%-17.6% ID at the end of infusion. After a washout phase that lasted 18-20 hr, incorporated radioactivity remained steadily associated with the tumor lesions until at least 42 hr after infusion (about 1.4%-11.1% ID). HPLC analysis indicated a virtually 100% first-pass hepatic deiodination of unincorporated [ 123I]IUdR (about 80%-95% ID recovered in the 42-hr urine). No significant uptake was detected in the bone marrow or in other normal dividing tissues. Conclusion: These results encourage further studies to enable dosimetric estimates, optimization of dose regimens, and examination of the therapeutic potential of Auger-electron-emitter-labeled IUdR in cancer therapy utilizing this type of approach.

Tumor targeting by intra-arterial infusion of 5-[123I]iodo-2'-deoxyuridine in patients with liver metastases from colorectal cancer

MARIANI, GIULIANO;VOLTERRANI, DUCCIO;DI STEFANO, ROSSELLA;FALCONE, ALFREDO;MOSCA, FRANCO;
1996

Abstract

We previously showed the tumor-targeting potential of the 125I-labeled thymidine analog 5-iodo-2′-deoxyuridine (IUdR) injected intratumorally in patients with high tumor-cell kinetics. In this study, we evaluated the tumor incorporation of [ 123I]IUdR infused intra-arterially in patients with liver metastases from colorectal cancer. Methods: Iodine-123-IUdR (110-300 MBq, 3-8 mCi, specific activity, 150-200 Ci/μmole) was infused into the hepatic artery of 16 patients with inoperable liver metastases over 30-45 min through a permanent intra-arterial catheter. A dynamic sequence during infusion, spot images, whole-body scans and SPECT acquisitions were recorded up to 42 hr. Blood and urine samples were obtained for biodistribution and HPLC analyses. Results: In the 14 patients with adequate tumor perfusion patterns, tumor uptake reached 2%-17.6% ID at the end of infusion. After a washout phase that lasted 18-20 hr, incorporated radioactivity remained steadily associated with the tumor lesions until at least 42 hr after infusion (about 1.4%-11.1% ID). HPLC analysis indicated a virtually 100% first-pass hepatic deiodination of unincorporated [ 123I]IUdR (about 80%-95% ID recovered in the 42-hr urine). No significant uptake was detected in the bone marrow or in other normal dividing tissues. Conclusion: These results encourage further studies to enable dosimetric estimates, optimization of dose regimens, and examination of the therapeutic potential of Auger-electron-emitter-labeled IUdR in cancer therapy utilizing this type of approach.
Mariani, Giuliano; DI SACCO, S; Volterrani, Duccio; DI LUCA, L; Buralli, S; DI STEFANO, Rossella; BARANOWSKA KORTYLEWICZ, J; Bonora, D; Matteucci, F; Ricci, S; Bellina, Cr; Falcone, Alfredo; Salvadori, Pa; Mosca, Franco; Adelstein, Sj; Kassis, Ai
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/205770
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