19-iodocholesterol and Neoplasm-Metastasis

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.

Topics: 19-Iodocholesterol; Absorbable Implants; Animals; Brachytherapy; Cell Line, Tumor; Chitosan; Cross-Linking Reagents; Female; Glutaral; Half-Life; Hydrogels; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Models, Biological; Neoplasm Metastasis; Oxidation-Reduction; Radiotherapy, Adjuvant; Secondary Prevention; Time Factors; Xenograft Model Antitumor Assays

I-131-6 beta-iodomethylnorcholesterol (NP-59) was used to localize mineralocorticoid-secreting adrenocortical carcinomas in two patients and functioning metastases in a third patient studied after the removal of the primary tumor. The presence of sufficient NP-59 activity within these lesions for discernable imaging is unusual and would not have been expected based on previous experience with other functioning and nonfunctioning carcinomas of the adrenal cortex. These cases serve to illustrate the variable spectrum of iodocholesterol uptake into adrenocortical malignancies and suggest that scintigraphic studies, preoperatively for localization and postoperatively to confirm the presence of recurrence or metastases, might be useful to identify and characterize these rare neoplasms.

Topics: 19-Iodocholesterol; Adrenal Cortex Neoplasms; Adult; Carcinoma; Catecholamines; Cholesterol; Female; Humans; Hyperaldosteronism; Iodine Radioisotopes; Male; Middle Aged; Mineralocorticoids; Neoplasm Metastasis; Radionuclide Imaging; Steroids; Tomography, X-Ray Computed

Topics: 19-Iodocholesterol; Adrenal Cortex; Adrenal Cortex Neoplasms; Adult; Carcinoma; Child; Female; Humans; Iodine Radioisotopes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Metastasis; Radionuclide Imaging; Time Factors