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Advisor(s)
Abstract(s)
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
.
Description
Keywords
Citation
Publisher
Instituto Politécnico do Porto. Escola Superior de Tecnologia da Saúde do Porto