Projects / Molecular structures to targeting tumor cells

Biotin derivatives


European Institute of Oncology

Fondazione Umberto Veronesi

The radioimmunotherapy (RIT) is a clinical technique allowing the radionuclide to bind a tumor-associated antigen on the membrane of tumor cells. This technique uses selective antibodies directly or indirectly radiolabeled. Monoclonal antibodies have the same properties as natural antibodies produced by the immune system. These MoAbs, able to recognize specific tumoral antigens present on the tumor, have been used by conventional RIT to transport a radioactive isotope that destroy the tumoral cells. The most important chelating agents are azamacrocycles. In particular, the tetraazamacrocycle DOTA (1,4,7,10-tetraaza-cyclododecane-1,4,7,10-tetraacetic acid), is the most used one. Actually, the so called pretargeting protocols, based on the Av/biotin system, are widely used in the clinical practice because the specific MoAbs are easily biotinilated and can bind the avidin with high affinity.Among them, the flexible three-steps method appeared especially useful for therapy of several types of tumours. These considerations prompted us to prepare a-biotinamido lysine derivatives by direct coupling of biotin with l-lysine suitably protected on the e-amino group. Then, the introduction of the bi-functional spacer and of two DOTA molecules should complete the synthetic steps. Aiming to ensure a fast synthetic approach, we decided to exploit the solid phase peptide synthesis (SPPS), routinely used in our laboratory of peptide chemistry. Pre-clinical studies in vitro were performed on the new derivatives, labeled with 90Y and 177Lu, at the European Institute of Oncology (Milano, Italy).


A. Pratesi, F. Bucelli, I. Mori, M. Chinol, A. Verdoliva, G. Paganelli, V. Rivieccio, L. Gariboldi, M. Ginanneschi ‘Biotin Derivatives Carrying Two Chelating DOTA Units. Synthesis, in Vitro Evaluation of Biotinidases Resistance, Avidin Binding, and Radiolabeling Tests’ J. Med. Chem., 2010, 53, 432–440.