Thesis
French
ID: <
10670/1.9s2nbm>
Abstract
Multiple myeloma accounts for 10% of hematological malignancies and still remains incurable despite medical progress. In this context, new targeting strategies represent a major step forward which can improve patient’s diagnosis and therapeutic monitoring. Antibodies are the most widely used targeting molecules but their pharmacokinetic and structural characteristics make their use suboptimal for imaging applications. Affitins are artificial affinity proteins with low molecular weight that exhibit comparable affinity and specificity to those of antibodies while being highly stable. These different characteristics make Affitins excellent candidates for a use in imaging as an alternative to antibodies. The aim of this thesis was therefore to investigate the interest of this new class of vector for phenotypic imaging of multiple myeloma. The first part of this work was devoted to the development and characterization of Affitins specific for CD38, a glycoprotein overexpressed by multiple myeloma cells. This study is still ongoing and will be followed by the preclinical evaluation of anti-CD38 Affitins. The second part of the thesis work was devoted to an imaging study based on the use of an anti- CD38 antibody radiolabelled with copper 64. The main objective of this study was to shed a first light on CD38 targeting for imaging and to serve as a point of comparison with similar studies that will be conducted with the anti- CD38 Affitins previously generated.