Prevention of tumor recurrence and distant metastasis formation in a breast cancer mouse model by biodegradable implant of ¹³¹I-norcholesterol

详细信息	查看全文 | 推荐本文 |

• 作者：Abdel Kareem Azab ; Jackie Kleinstern ; Victoria Doviner ; Boris Orkin ; Morris Srebnik ; Aviram Nissan ; Abraham Rubinstein
• 关键词：Crosslinked chitosan ; Biodegradable implant ; Brachytherapy ; Breast cancer ; Locoregional recurrence ; Minimal residual disease
• 刊名：Journal of Controlled Release
• 出版年：2007
• 期刊代码：25_01683659
• 类别：pha
• 出版时间：6 November 2007
• 卷：123
• 期：2
• 页码：116-122
• 文件大小：1050 K

摘要

Brachytherapy has many potential roles in cancer therapy. However, major constraints are associated with placement and removal procedures of the brachytherapy machinery. An attractive approach would be the use of a biodegradable implant loaded with a radioisotope, thus enabling targeted radiotherapy, while reducing the need for surgical procedures for the removal of brachytherapy hardware. In this study, crosslinked chitosan (Ct) hydrogels were prepared and loaded with ¹³¹I-norcholesterol (¹³¹I–NC). The radioactive hydrogels (¹³¹I–NC–Ct) were implanted adjacent to 4T1 cell-induced tumors in two different xenograft mice models either as primary therapy or surgical adjuvant therapy of breast cancer. Non-treated mice and mice implanted with naive (non-radioactive) hydrogels served as control groups.

In the primary therapy model, the progression rate of the tumor was delayed by two weeks compared with the non-treated and the naive-implant control animals, resulting in a one-week extension in the survival of the treated animals. In the adjuvant therapy model, for the treatment of minimal residual disease, ¹³¹I–NC–Ct implants were able to prevent 69%of tumor recurrence, and to prevent metastatic spread resulting in long-term survival, compared with 0%long-term survival of the non-treated and the naive control groups.

Imaging of the hydrogel's in vivo elimination revealed a first order process with a half-life of 14 days. The degradation was caused by oxidation of the Ct as was assessed by in vitro H&E stain.

Biodegradable radioactive implants are suggested as a novel platform for the delivery of brachytherapy. This radiotherapy regimen may prevent locoregional recurrence and metastatic spread after tumor resection.