Abstract |
The development of alternative therapies for melanoma treatment is of great interest as long-term tumour regression is not achieved with new targeted chemotherapies on selected patients. We previously demonstrated that radioiodinated heteroarylcarboxamide ([131I] ICF01012) induced a strong anti-tumoural effect by inhibiting both primary tumour growth and dissemination process in a B16BL6 melanoma model. In our study, we show that a single injection of [131I] ICF01012 (ranging from 14.8 to 22.2 MBq) was effective and associated with low and transient haematological toxicity. Concerning pigmented organs, cutaneous melanocytes and skin were undamaged. In 30% of treated animals, no histological alteration of retina was observed, and in the remaining 70%, damages were restricted to the optic nerve area. Using the Medical Internal Radiation Dose methodology, we determined that the absorbed dose in major organs is very low (<4 Gy) and that a delivery of 30 Gy to the tumour is sufficient for an effective anti-tumoural response. Molecular analyses of treated tumours showed a strong radiobiological effect with a decrease in proliferation, survival and pro-angiogenic-related markers and an increase in tumour suppressor gene expression, melanogenesis and anti-angiogenic markers. All these features are in accordance with a tumour cell death mechanism that mainly occurs by mitotic catastrophe and provide a better understanding of in vivo anti-tumoural effects of [131I] radionuclide. Our findings raise [131I] ICF01012 a good candidate for disseminated melanoma treatment and strongly support transfer of [131I] ICF01012 to clinical trial.
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Authors | Françoise Degoul, Michèle Borel, Nathalie Jacquemot, Sophie Besse, Yves Communal, Florence Mishellany, Janine Papon, Frédérique Penault-Llorca, Denise Donnarieix, Michel Doly, Lydia Maigne, Elisabeth Miot-Noirault, Anne Cayre, Jacques Cluzel, Nicole Moins, Jean-Michel Chezal, Mathilde Bonnet |
Journal | International journal of cancer
(Int J Cancer)
Vol. 133
Issue 5
Pg. 1042-53
(Sep 01 2013)
ISSN: 1097-0215 [Electronic] United States |
PMID | 23404099
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2013 UICC. |
Chemical References |
- Iodine Radioisotopes
- Melanins
- N-(2-diethylaminoethyl)-6-iodoquinoxaline-2-carboxamide
- Quinoxalines
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Topics |
- Animals
- Cell Cycle
(radiation effects)
- Humans
- Iodine Radioisotopes
(therapeutic use)
- Male
- Melanins
(antagonists & inhibitors)
- Melanoma, Experimental
(metabolism, pathology, radiotherapy)
- Mice
- Mice, Inbred C57BL
- Quinoxalines
(therapeutic use)
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