Evaluation of 99mTc-Sestamibi as a potential tool to investigate PgP activity in inflammation

Abstract

In the XXI Century’s Society the scientific investigation process has been rowing steadily, and the field of the pharmaceutical research is one of the most enthusiastic and relevant. Here, it is very important to correlate bserved functional alterations with possibly modified drug bio distribution patterns. Cancer, inflammation and infection are processes that induce many olecular intermediates like cytokines, chemokines and other chemical complexes that an alter the pharmacokinetics of many drugs. One cause of such changes is hought to be the modulator action of these complexes in the P-Glycoprotein activity, because they can act like inducers/inhibitors of MDR-1 expression. This protein results from the expression of MDR-1 gene, and acts as an ATP energy-dependent efflux pump, withtheir substrates including many drugs, like antiretrovirals, anticancers, anti-infectives, immunosuppressants, steroids or opioids. Because of the lack of methods to provide helpful information in he investigation of in vivo molecular changes in Pgp activity during fection/infl ammation processes, and its value in the explanation of the altered drug harmacokinetic, this paper want to evaluate the potential utility of 99m Tc-Sestamibi scintigraphy during this kind of health sciences investigation. Although the aim is indeed to create a technique to the in vivo study of Pgp activity, this preliminary Project only reaches the in vitro study phase, assumed as the first step in a n evaluation period for a new tool development. Materials and Methods: For that reason , we are performing in vitro studies of influx and efflux of 99m Tc - Sestamibi ( that is a substrate of Pgp) in hepatocytes cell line (HepG2). We are interested in clarify the cellular behavior of this radiopharmaceutical in Lipopolysaccharide(LPS) stimulated cells ( well known in vitro model of inflammation) to possibly approve this methodology. To validate the results, the Pgp expression will be finally evaluated using Western Blot technique. Results: Up to this moment , we still don’t have the final results, but we have already enough data to let us believe that LPS stimulation induce a downregulation of MDR - 1, and consequently Pgp, which could conduce to a prolonged retention of 99m Tc - Sestamibi in the inflamed cells . Conclusions: If and when this methodology demonstrate the promising results we expect, one will be able to con clude that Nuclear Medicine is an important tool to help evidence based research also on this specific field