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

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Abstract

Tissue 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 of 131I and 131I-ixolaris in tumor-free and melanoma-bearing mice; III) evaluate whether 131I-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 free 131I or 131I-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 of 131I-ixolaris at the same day the animals were inoculated with melanoma cells. In the second group, D15, a single-dose of 9.25 MBq of 131I-ixolaris or free 131I 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 of 131I-ixolaris or 131I. In vitro studies demonstrated that 131I-ixolaris is stable for up to 24 h and retains its inhibitory activity on blood coagulation. Biodistribution analysis and metastasis assays showed that all treatment regimens with 131I-ixolaris were effective, being the double-treatment (D1/D15) the most effective one. Remarkably, treatment with free 131I showed no anti-metastatic effect. 131I-ixolaris is a promising theranostic agent for metastatic melanoma.

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Acknowledegements

The Brazilian National Council for Scientific and Technological Development (CNPq), The State of Rio de Janeiro Research Foundation (FAPERJ), and the Coordination for the Improvement of Higher Education Personnel (CAPES) supported this investigation.

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Authors and Affiliations

  1. Departamento de Radiologia, Faculdade de Medicina, Laboratório de Marcação de Células E Moléculas, Universidade Federal Do Rio de Janeiro, Rio de Janeiro, Brasil

    Thiago Barboza, Priscylla da Costa Medeiros, Bianca Gutfilen & Sergio Augusto Lopes de Souza

  2. Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal Do Rio de Janeiro, Rio de Janeiro, Brasil

    Tainá Gomes & Robson Q. Monteiro

  3. Centro Nacional de Bioimagem E Biologia Estrutural, Bloco M, Unidade 2, Centro de Ciências da Saúde, Universidade Federal Do Rio de Janeiro, Rio de Janeiro, Brasil

    Isalira Peroba Ramos & Sergio Augusto Lopes de Souza

  4. Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Bethesda, USA

    Ivo Francischetti

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  1. Thiago Barboza
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  2. Tainá Gomes
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Correspondence to Sergio Augusto Lopes de Souza.

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Barboza, T., Gomes, T., da Costa Medeiros, P. et al. Development of 131I-ixolaris as a theranostic agent: metastatic melanoma preclinical studies. Clin Exp Metastasis 37, 489–497 (2020). https://doi.org/10.1007/s10585-020-10036-0

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  • DOI: https://doi.org/10.1007/s10585-020-10036-0

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