Krebswissenschaft und -therapie

Promising Pre-clinical Validation of Targeted Radionuclide Therapy Using a [131I] Labelled Iodoquinoxaline Derivative for an Effective Melanoma Treatment

Abstract

Bonnet-Duquennoy M, Papon J, Mishellany F, Denoyer D, Labarre P, Guerquin-Kern JL, Penault-llorca F, Madelmont JC, Miot-Noirault E, Cayre A, Chezal JM and Moins N

Targeted internal radionuclide therapy (TRT) would be an effective alternative to current therapies for disseminated melanoma treatment. At our institution, a class of iodobenzamides has been developed as potent melanomaseeking agents. This review described the preclinical validations of a quinoxaline derivative molecule (ICF01012) as tracer for TRT application. It was selected for its high, specific and long-lasting uptake in tumour with rapid clearance from non-target organs providing suitable dosimetry parameters for TRT. Extended in vivo study of metabolic profiles confirmed durable tumoural concentration of the unchanged molecule form. Moreover melanin specificity of ICF01012 was determined by binding assay with synthetic melanin and in vivo by SIMS imaging. Then, we showed in vivo that [131I] ICF01012 treatment drastically inhibited growth of B16F0, B16Bl6 and M4Beu tumours whereas [131I] NaI or unlabelled ICF01012 treatment was without significant effect. Histological analysis showed that residual tumour cells exhibit a significant loss of aggressiveness after treatment. This anti-tumoural effect was associated with a lengthening of the treated-mice survival time and an inhibition of lung dissemination for B16Bl6 model. Results presented here support the concept of TRT using a [131I] labelled iodoquinoxaline derivative for an effective melanoma treatment.