1: Radiother Oncol. 2006 Sep 13; [Epub ahead of print]

Preclinical safety and antitumor efficacy of insulin combined with irradiation.

Jordan BF, Beghein N, Crokart N, Baudelet C, Gregoire V, Gallez B.

Laboratory of Biomedical Magnetic Resonance,; Laboratory of Medicinal Chemistry
and Radiopharmacy, and.

BACKGROUND AND PURPOSE: We have previously reported that insulin significantly
enhances tumor oxygenation (pO(2)) and increases radiation-induced tumor
regrowth delay in experimental models. Considering the large radiosensitizing
effect, clinical trials might be envisioned. The aim of the present pre-clinical
study was to obtain a more complete set of safety and efficacy data which would
further justify the commencement of such clinical trials. MATERIAL AND METHODS:
Toxicity on normal (early and late-responding) tissues was measured by the
intestinal crypt regeneration assay and the late leg contracture assay. Efficacy
in terms of enhancement of pO(2) (measured by in vivo EPR oximetry) and increase
in radiation-induced tumor regrowth delay was evaluated with a dose-response
study on mice bearing FSaII fibrosarcoma. RESULTS: The effect on regrowth delay
was directly correlated with the effect on the tumor pO(2), with a maximal
effect using 400mUkg(-1) insulin. Importantly, there was no increase in the
radiation toxicity for normal tissues. Finally, we found that the hypoglycaemia
induced by insulin can be corrected by simultaneous glucose infusion without
modification of efficacy. CONCLUSION: Insulin here demonstrated a therapeutic
gain and a lack of toxicity to normal tissues. The results of this study fully
justify further larger preclinical assays such as the use of fractionated
irradiation and a tumor control dose assay, before determining the utility of
insulin as a radiosensitizer for human patients in the clinic.

PMID: 16978721 [PubMed - as supplied by publisher]

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