Dr. Cyril Papamicaël
Dr. Cyril Papamicaël
INSA-Rouen, France
Title: Delivering FLT to the Central Nervous System by means of a Promising Dihydroquinoline-based Targeting System
Almost 100% of large neuro-therapeutic molecules and over 95% of small therapeutic molecules cannot go into the central nervous system (CNS). Radiotracers are also included in these molecules: so, brain imaging is also concerned for many brain diseases at an early stage. We are aiming at targeting drugs and radiotracers into the CNS by means of a redox chemical delivery system based on a 1,4-dihydroquinoline carrier. Our research work is now mainly focused on the delivery of radiotracers, and more particularly MIBG and FLT. Iodine-radiolabeled MIBG used to check for some kinds of neuroendocrine tumors, including pheochromocytomas and neuroblastomas. MIBG is a tracer of the monoamine uptake and storage function involved in APUD system tumors, in organs with adrenergic innervation and the brain. [18F]FLT is a reliable PET of cell proliferation. The latter can be used in high grade gliomas for PET imaging since the blood brain barrier (BBB) protecting the brain is altered. Conversely, in low grade gliomas [18F]FLT cannot cross the BBB preventing its use in PET imaging to detect brain tumors at an early stage. To this end, we have decided to covalently link either MIBG or FLT to a set of 1,4-dihydroquinoline systems to enable the passage of the BBB. To determine the best carrier, we prepared radiolabeled [11C] 1,4-dihydroquinoline which were injected into rats. Preliminary promising results will be given with MIBG and, mainly, with FLT.
Dr. Cyril Papamicaël obtained his PhD under the guidance of Professor G. Quéguiner and G. Dupas at the University of Rouen (France) in 1997. His PhD concerned the synthesis and functionalization reaction of carbolines by means of lithiation reactions. He then spent two years working with Professor A. Gossauer at the University of Fribourg (Switzerland). During the course of his research work, he was interested in the synthesis of metallo-porphyrin models for light-harvesting studies. Thereafter, he was engaged in a postdoctoral work for two years with Professor C.J. Schofield (non-penicillin inhibitors) and Professor Jack E. Baldwin (penicillin derivatives inhibitors) at the University of Oxford (United-Kingdom) to synthesize and study metallo--lactamase inhibitors. He was finally recruited on a permanent researcher position at INSA-university of Rouen. He first worked with Pr G. Dupas whose the main research field focused with biomimetic models. Thus, he studied for example the amide bond formation using heterocyclic amine and acid receptors. After G. Dupas retirement, he has changed his research area. He is now both interested in the design ofAcetylcholinesterase inhibitors and the chemistry devoted to medical imaging. His research work concerns the synthesis and development of new redox chemical delivery systems to target drugs and radiotracers into the brain. He has several collaborations, both with academics (France, Australia, UK) and with private companies or independent institutions (PolyIntell, centre Henri Becquerel Rouen, VFP-therapies). 40 publications, 35 communications (posters or oral communications), 2 proceedings, 1 patent (PCT Int..Appl (2014), WO 2014114742 A1 20140731).