Synthesis, radiolabeling and preliminary in vivo evaluation of multimodal radiotracers for PET imaging and targeted radionuclide therapy of pigmented melanoma.

Abstract

Melanin pigment represents an attractive target to address specific treatment to melanoma cells, such as cytotoxic radionuclides. However, less than half of the patients have pigmented metastases. Hence, specific marker is required to stratify this patient population before proceeding with melanin-targeted radionuclide therapy. In such a context, we developed fluorinated analogues of a previously studied melanin-targeting ligand, N-(2-diethylaminoethyl)-6-iodoquinoxaline-2-carboxamide (ICF01012). These latter can be labeled either with (18)F or (131)I/(125)I for positron emission tomography imaging (melanin-positive patient selection) and targeted radionuclide therapy purposes. Here we describe the syntheses, radiosyntheses and preclinical evaluations on melanoma-bearing mice model of several iodo- and fluoro(hetero)aromatic derivatives of the ICF01012 scaffold. After preliminary planar gamma scintigraphic and positron emission tomography imaging evaluations, [(125)I]- and [(18)F]-N-[2-(diethylamino)ethyl]-4-fluoro-3-iodobenzamides ([(125)I]4, [(18)F]4) were found to be chemically and biologically stable with quite similar tumor uptakes at 1 h p.i. (9.7 ± 2.6% ID/g and 6.8 ± 1.9% ID/g, respectively).

• Authors: Emilie M F Billaud, Aurélie Maisonial-Besset, Latifa Rbah-Vidal, Aurélien Vidal, Sophie Besse, Jean-Baptiste Béquignat, Caroline Decombat, Françoise Degoul, Laurent Audin, Jean-Bernard Deloye, Frédéric Dollé, Bertrand Kuhnast, Jean-Claude Madelmont, Sébastien Tarrit, Marie-Josèphe Galmier, Michèle Borel, Philippe Auzeloux, Elisabeth Miot-Noirault, Jean-Michel Chezal
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 92 Pg. 818-38 (Mar 06 2015) ISSN: 1768-3254 [Electronic] France
• PMID: 25637883 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Chemical References

• Fluorine Radioisotopes
• Iodine Radioisotopes
• Radioactive Tracers

Topics

• Animals
• Disease Models, Animal
• Fluorine Radioisotopes (chemistry)
• Humans
• Iodine Radioisotopes (chemistry)
• Male
• Melanoma, Experimental (diagnosis, drug therapy)
• Mice
• Mice, Inbred C57BL
• Molecular Imaging
• Molecular Structure
• Positron-Emission Tomography
• Radioactive Tracers