Targeted radionuclide therapy of melanoma: anti-tumoural efficacy studies of a new 131I labelled potential agent.
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| Abstract |
In recent years, there has been dramatic worldwide increase in incidence of malignant melanoma. Although localised disease is often curable by surgical excision, metastatic melanoma is inherently resistant to most treatments. In this context, targeted radionuclide therapy could be an efficient alternative. After pharmacomodulation study, we selected a quinoxaline derivative molecule (ICF01012) for its high, specific and long-lasting uptake in melanoma with rapid clearance from nontarget organs providing suitable dosimetry parameters for targeted radiotherapy. Aim of this study was to investigate, in vivo, efficacy of [(131)I]ICF01012 on nonmetastatic B16F0, metastatic B16Bl6 or human M4Beu melanoma tumours. First, colocalisation of ICF01012 with melanin by SIMS imaging was observed. Second, we showed that treatment drastically inhibited growth of B16F0, B16Bl6 and M4beu tumours whereas [(131)I]NaI or unlabelled ICF01012 treatment was without significant effect. Histological analysis and measure of PCNA proliferation marker expression showed that residual B16 tumour cells exhibit a significant loss of aggressiveness after treatment. This effect is associated with a lengthening of the treated-mice survival time. Moreover, with B16Bl6 model, 55% of the untreated mice had lung metastases whereas no metastasis was counted on treated group. Our data demonstrated a strong anti-tumoural effect of [(131)I]ICF01012 for radionuclide therapy on murine and human in vivo pigmented melanoma models, whatever their dissemination profiles and their melanin content be. Further studies will attempt to optimise therapy protocol by increasing the balance between the anti-tumoural effect and the safety on non-target organs.
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| Authors | Mathilde Bonnet-Duquennoy, Janine Papon, Florence Mishellany, Pierre Labarre, Jean-Luc Guerquin-Kern, Ting-Di Wu, Maryline Gardette, Jean Maublant, Frédérique Penault-Llorca, Elisabeth Miot-Noirault, Anne Cayre, Jean-Claude Madelmont, Jean-Michel Chezal, Nicole Moins |
| Journal | International journal of cancer (Int J Cancer) Vol. 125 Issue 3 Pg. 708-16 (Aug 01 2009) ISSN: 1097-0215 [Electronic] United States |
| PMID | 19437532 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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