• probes
• fluorescent
• PET
• indolylglyoxylamides
• TSPO

ABSTRACT

The 18kDa Translocator Protein (TSPO) is mainly located at the contact sites between the outer and the inner mitochondrial membranes, and is strictly associated with a number of proteins to form the mitochondrial permeability transition pore (MPTP). It is involved in a variety of biological processes including cholesterol transport, steroidogenesis, cell growth and differentiation, apoptosis induction, and regulation of immune functions.

The expression of TSPO is ubiquitary in peripheral tissues (steroid producing tissues, liver, heart, kidney, lung, immune system) and in the central nervous system is mainly located in glial cells and in neurons. TSPO is up-regulated in a number of neuropathologies, Huntington’s and Alzheimer’s diseases, tumors etc..

Consequently, TSPO has been suggested as a promising diagnostic marker to image and measure the TSPO expression and distribution levels, and thus for evaluation of disease progression by means of specific fluorescent or radiolabeled ligands.

The aim of this work is to synthesize and biological characterize a series of 2-phenylindol-3-ylglyoxylamides, and to test their validity as new TSPO probes.
Compound 1 is characterized by the presence of a chemoreactive isothiocyanate group and by the NBD-fluorescent moiety. Compounds 2 and 3 are characterized by the presence of (1,4,7-triazonane-1,4,7-triyl)triacetic acid group (NOTA) and were synthesize to prepare and evaluate Ga-68 complexes as potential PET agents for measurement of TSPO.