Pentavalent antimonials such as meglumine antimoniate (
MA) are the primary treatments for leishmaniasis, a complex disease caused by protozoan parasites of the genus
Leishmania. Despite over 70 years of clinical use, their mechanisms of action, toxicity and pharmacokinetics have not been fully elucidated. Radiotracer studies performed on animals have the potential to play a major role in pharmaceutical development. The aims of this study were to prepare an antimony radiotracer by neutron irradiation of
MA and to determine the biodistribution of
MA in healthy and
Leishmania (Leishmania)
infantum
chagasi-infected mice.
MA (Glucantime®) was neutron irradiated inside the
IEA-R1 nuclear reactor, producing two radioisotopes,
122Sb and
124Sb, with high radionuclidic purity and good specific activity. This irradiated compound presented anti-leishmanial activity similar to that of non-irradiated
MA in both
in vitro and
in vivo evaluations. In the biodistribution studies, healthy mice showed higher uptake of antimony in the liver than infected mice and elimination occurred primarily through biliary excretion, with a small proportion of the drug excreted by the kidneys. The serum kinetic curve was bi-exponential, with two compartments: the central compartment and another compartment associated with drug excretion. Radiotracers, which can be easily produced by neutron irradiation, were demonstrated to be an interesting tool for answering several questions regarding antimonial pharmacokinetics and chemotherapy.
