TY - JOUR
T1 - Prevention of tumor recurrence and distant metastasis formation in a breast cancer mouse model by biodegradable implant of 131I-norcholesterol
AU - Azab, Abdel Kareem
AU - Kleinstern, Jackie
AU - Doviner, Victoria
AU - Orkin, Boris
AU - Srebnik, Morris
AU - Nissan, Aviram
AU - Rubinstein, Abraham
N1 - Funding Information:
The results reported here are included in the dissertation project of A. K. Azab in partial fulfillment of his PhD degree requirements of The Hebrew University of Jerusalem. The study has been presented in part in the Gordon Conference on Drug Carriers in Medicine and Biology, Montana USA, 2006. The study was supported by a research grant # 1358/05 from the Israeli Science Foundation, by a research grant # 2005237 from the United States–Israel Binational Science Foundation, by the Robert Szold Fund and the Julius Oppenheimer Endowment. A. Rubinstein is affiliated with the David R. Bloom Center of Pharmacy.
PY - 2007/11/6
Y1 - 2007/11/6
N2 - 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.
AB - 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.
KW - Biodegradable implant
KW - Brachytherapy
KW - Breast cancer
KW - Crosslinked chitosan
KW - Locoregional recurrence
KW - Minimal residual disease
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U2 - 10.1016/j.jconrel.2007.07.014
DO - 10.1016/j.jconrel.2007.07.014
M3 - Article
C2 - 17854940
AN - SCOPUS:35348920801
SN - 0168-3659
VL - 123
SP - 116
EP - 122
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 2
ER -