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Radiosensitivity of Rat Mammary Tumors Correlates With Early Vessel Changes Assessed by Power Doppler Sonography

Institut National de la Santé et de la Recherche Médicale E 0211 (F.D., P.B., L.P., O.l.F.) and Institut National de la Santé et de la Recherche Médicale Unité 316, Institut Fédératif de Recherche 120 (F.T.), Centre Hospitalier Universitaire Bretonneau, Tours, France.

Address correspondence and reprint requests to Fabrice Denis, MD, MSc, Institut National de la Santé et de la Recherche Médicale E 0211, CORAD, Centre Hospitalier Universitaire Bretonneau, 37044 Tours, France. E-mail: fcdenis{at}club-internet.fr.

Objective. To investigate the changes occurring in the vascularization of tumors during irradiation, we used a model of autochthonous mammary tumors in rats and assessed early vascular changes after irradiation by power Doppler sonography. Methods. Mammary tumors were induced in 24 female Sprague Dawley rats by a single subcutaneous injection of N-nitroso N-methyl urea. After tumor areas reached 1 cm², the animals received a single fraction of 18-Gy radiation or intraperitoneal saline injection. Power Doppler sonographic quantification of detected vessels was performed 1 day before irradiation and 7 days after the use of a power Doppler index of 5 different tumor imaging planes. Final tumor shrinkage was compared with early changes in the power Doppler index. Not all tumors regressed in a similar fashion. Radiosensitive tumors were defined as tumors with a greater than 50% decrease in baseline area 28 days after irradiation, whereas radioresistant tumors were tumors with a less than 50% decrease in baseline area. Statistical analysis was performed by the Mann-Whitney U test. Results. Tumor area changes were similar in radioresistant and radiosensitive tumors 7 days after irradiation (–41% and –35%, respectively; P > .05, not significant), whereas reduction in the power Doppler index was significantly greater in radiosensitive tumors (mean value, –63%) than in radioresistant tumors (mean value, –12%) (P = .001). Late tumor regrowth was correlated with day 7 power Doppler index changes (P = .009). A 40% reduction in the power Doppler index at day 7 distinguished 8 of 9 radiosensitive tumors and 8 of 9 radioresistant tumors (P = .003). Conclusions. This study suggests that early changes in tumor perfusion as assessed by power Doppler sonography after tumor irradiation may precede the long-term tumor regression.

Key Words: angiogenesis • Doppler sonography • radiotherapy

Abbreviations: PDI, power Doppler index • ROC, receiver operating characteristic • VEGF, vascular endothelial growth factor

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