Page 163 - 00. Complete Version - Progress Report IPEN 2014-2016

Nuclear Science and Technology | Progress Report 163

that the athletes did not report the intake of be caused by ionizing radiation.
supplement, this increase suggests the need
of nutritional reevaluation. Establishment of iron concentrations
in whole blood of different mice
Development of 177Lu-DOTA-Dendrimer strains: an alternative for pre-
and determination of its effect on clinical tests of news drugs
metal and ion levels in tumor tissue

Nowadays, Brazil’s pharmaceutical companies
Dendrimers are synthetic nanomolecules with are testing iron compounds to attend popula-
well-defined chemical structures. Different tions of low income. Drug development is com-
strategies have been used for radiolabeling plex and extensive (it usually takes years to be
dendrimers with different radioisotopes. There approved and marketed). It is a very expensive
is a variety of dendrimers, and each one has bi- endeavor undertaken by scientists and phar-
ological properties such as polyvalency, self-as- maceutical companies. Investment in new
sembling, electrostatic interactions, chemical drugs requires several steps and it is manda-
stability and low cytotoxicity. These varied tory to carry out various screening tests before
characteristics make dendrimers a good choice starting the studies in human being. These
in the medical field for several medical appli- tests are called pre-clinical and comprise the
cations. In this study, the aim was to conju- following fields of study: biopharmaceutical
gate dendrimers with 177Lu, to observe the (formulation), in vitro pharmacological stud-
in vivo behavior of the labeled compound and ies and in animals in vivo tests for the evalua-
to measure the elementary changes in tumor tion of potential clinical efficacy. While in vitro
tissue that could be caused by ionizing radia- tests are used to identify the pharmacologi-
tion. PAMAM G4 dendrimers conjugated with cal properties (pharmacodynamics effects) of
DOTA were labeled with 177Lu. The radiola- a new drug, in vivo tests are performed in or-
beled compound was characterized and its der to evaluate the safety of new drugs prior
stability was evaluated by reverse phase high to any clinical trial with humans. Considering
performance liquid chromatography. Radiola- the low cost, easy handling and simplicity re-
beling yield was > 98% and stable for 24 hours. lated to the legal implications, the pre-clinical
Biodistribution studies of 177Lu-DOTA-den- tests are usually performed in mice (small size
drimers in C57BL/6 melanoma-bearing mice animal model). There are several mice strains
showed blood clearance with hepatic and re- developed for the research of new drugs. The
nal depuration and tumor uptake. The concen- most used strains are C57BL/6J, A/J and BAL-
trations of Br, Ca, Cl, Fe, K, Mg, Na, Rb, S, and Zn B/c. Some of them are inbreed for high and
were determined in tumor tissues of C57BL/ low antibody-producer (HIII and LIII), some
J6 mice treated with 177Lu-DOTA dendrimers for maximum and minimum inflammatory
and in untreated mice. The results showed de- response AIRMAX and AIRMIN, some for au-
creased concentrations of Br (62%), Ca (24%), toimmune diseases (B10.RIII, NZW and NZB),
Cl (51%), K (12%), and Na (60%) and increased others are mutants for muscular dystrophy
concentrations of Fe (8%), Mg (28%), Rb (100%), (SJL/J and Dm dmdx/J). This study aims to de-
S (6%), and Zn (4%) in tumor tissues of mice termine the Fe concentration in whole blood
treated with 177Lu-DOTA-dendrimers. These of these distinct mice strains. The results will
data may be useful to evaluate changes in tu- be correlated with human whole blood esti-
mor tissues as indicators of damage that could mation for checking the similarities, a funda-