Chemoradionuclide Therapy with 186Re-labeled Liposomal Doxorubicin in Combination with Radiofrequency Ablation for Effective Treatment of Head and Neck Cancer in a Nude Rat Tumor Xenograft Model

Chemoradionuclide Therapy with 186Re-labeled Liposomal Doxorubicin in Combination with Radiofrequency Ablation for Effective Treatment of Head and Neck Cancer in a Nude Rat Tumor Xenograft Model
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DOI:
10.1148/radiol.11110361
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发表时间:
2011-12-01
期刊:
影响因子:
19.7
通讯作者:
Goins, Beth A.
Goins, Beth A.
中科院分区:
医学1区
文献类型:
--
作者:
Soundararajan, Anuradha;Dodd, Gerald D., III;Goins, Beth A.

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Purpose: To determine the therapeutic efficacy of rhenium 186 (Re-186)-labeled PEGylated liposomal doxorubicin (Re-186-liposomal doxorubicin) in combination with radiofrequency (RF) ablation of human bead and neck squamous cell carcinoma (HNSCC) xenograft in nude rats.Materials and Methods: This investigation was approved by the animal care committee. Sixty nude rats with subcutaneously implanted HNSCC xenografts (six per group) were treated with (a) RF ablation (70 degrees C for 5 minutes), (b) PEGylated liposomes, (c) liposomal doxorubicin, (d) Re-186-PEGylated liposomes (1295 MBq/kg), (e) Re-186-liposomal doxorubicin (555 MBq/kg), (f) PEGylated liposomes plus RI? ablation, (g) liposomal doxorubicin plus RF ablation, (6) Re-186-PEGylated liposomes plus RF ablation, or (i) Re-186-liposomal doxorubicin plus RF ablation. Six rats did not receive any treatment (control group). Tumor uptake in Re-186 therapy groups was monitored with small-animal single photon emission computed tomography for 5 clays. Therapeutic efficacy was monitored for 6 weeks with measurement of tumor volume, calculation of the percentage injected dose of fluorine 18 fluorodeoxyglucose (FDG) in tumor from small-animal positron emission tomography (PET) images, and determination of viable tumor volume at histopathlogic examination. Significant differences between groups were determined with analysis of variance.Results: The average tumor volume (+/- standard deviation) on the day of therapy was 1.32 cm(3) +/- 0.17. At. 6 weeks after therapy, control of tumor growth was better with Re-186-liposomal doxorubicin than with liposomal doxorubicin alone (tumor volume, 2.26 cm(3) +/- 0.89 vs 5.43 cm(3) +/- 0.93, respectively; P < .01). The use of RF ablation with liposomal doxorubicin and Re-186-liposomal doxorubicin further improved tumor control (tumor volume, 2.05 cm(3) +/- 1.36 and 1.49 cm(3) +/- 1.47, respectively). The tumor growth trend correlated with change in percentage of injected dose of FDG in tumor for all groups (R-2 = 0.85, P < .001). Viable tumor volume was significantly decreased in the group treated with Re-186-liposomal doxorubicin plus RF ablation (0.54 cm(3) +/- 0.38: P < .001 vs all groups except Re-186-liposornal doxorubicin alone).Conclusion: Triple and dual therapies had an observable trend (Re-186-liposomal doxorubicin plus RF ablation > Re-186-liposomal doxorubicin > liposomal doxorubicin plus RF ablation > liposomal doxorubicin) of improved tumor growth control and decreased viable tumor compared with other therapies. FDG PET could be used as a noninvasive surrogate marker for tumor growth and viability in this tumor model. (C) RSNA, 2011