Development of 131 I-ixolaris as a theranostic agent: metastatic melanoma preclinical studies

AbstractTissue factor (TF), a blood coagulation protein, plays an important role in tumor growth, invasion, and metastasis. Ixolaris, a tick-derived non-immunogenic molecule that binds to TF, has demonstrated in vivo inhibitory effect on murine models of melanoma, including primary growth and metastasis. This work aimed to: I) develop an efficient and stable labeling technique of ixolaris with Iodine-131(131I); II) compare the biodistribution of131I and131I-ixolaris in tumor-free and melanoma-bearing mice; III) evaluate whether131I-ixolaris could serve as an antimetastatic agent. Ixolaris radioiodination was performed using iodogen, followed by liquid paper chromatography. Labeling stability and anticoagulant activity were measured. Imaging studies were performed after intravenous administration of free131I or131I-ixolaris in a murine melanoma model employing the B16-F10 cell line. Animals were divided in three experimental groups: the first experimental group, D0, received a single-dose of 9.25  MBq of131I-ixolaris at the same day the animals were inoculated with melanoma cells. In the second group, D15, a single-dose of 9.25  MBq of131I-ixolaris or free131I was applied into mice on the fifteenth day after the tumor induction. The third group, D1-D15, received two therapeutic doses of 9.25  MBq of131I-ixolaris or131I. In vitro studies demonstrated that131I-ixolaris is stable for up to 24  h and retains its inhibitory activity on blood coagulation. Biodistribution analysi...
Source: Clinical and Experimental Metastasis - Category: Cancer & Oncology Source Type: research