| Abstract | 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 (131)I-norcholesterol ((131)I-NC). The radioactive hydrogels ((131)I-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, (131)I-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. |
| Authors | Abdel Kareem Azab, Jackie Kleinstern, Victoria Doviner, Boris Orkin, Morris Srebnik, Aviram Nissan, Abraham Rubinstein
(Affiliation: Department of Pharmaceutics, The Hebrew University of Jerusalem, School of Pharmacy, Jerusalem, Israel.)
|
| Journal | Journal of controlled release : official journal of the Controlled Release Society
(J Control Release)
Vol. 123
Issue 2
Pg. 116-22
(Nov 6 2007)
ISSN: 1873-4995 Netherlands |
| PMID | 17854940
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Cross-Linking Reagents
- Hydrogels
- I-norcholesterol
- Glutaral
- 19-Iodocholesterol
- Chitosan
|
| Topics |
- 19-Iodocholesterol
(administration & dosage, analogs & derivatives, chemistry)
- Absorbable Implants
- Animals
- Brachytherapy
(methods)
- Cell Line, Tumor
- Chitosan
(chemistry, metabolism)
- Cross-Linking Reagents
(chemistry)
- Female
- Glutaral
(chemistry)
- Half-Life
- Hydrogels
- Mammary Neoplasms, Experimental
(pathology, radiotherapy, surgery)
- Mice
- Mice, Inbred BALB C
- Models, Biological
- Neoplasm Metastasis
(prevention & control)
- Oxidation-Reduction
- Radiotherapy, Adjuvant
- Recurrence
(prevention & control)
- Time Factors
- Xenograft Model Antitumor Assays
|
