Page 16 - PR 2014 2016 07 Nuclear Science and Technology

158 Nuclear Science and Technology | Progress Report

mance and, in more severe cases, it can evolve be useful to evaluate changes in tumor tissues
to neurodegenerative disorders. Considering as indicators of damage that could be caused
that the athletes did not report the intake of by ionizing radiation.
supplement, this increase suggests the need
of nutritional reevaluation. Establishment of iron concentrations
in whole blood of different mice
Development of Lu-DOTA-Dendrimer strains: an alternative for pre-
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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 popu-
well-defined chemical structures. Different lations of low income. Drug development is
strategies have been used for radiolabeling complex and extensive (it usually takes years
dendrimers with different radioisotopes. There to be approved and marketed). It is a very ex-
is a variety of dendrimers, and each one has pensive endeavor undertaken by scientists and
biological properties such as polyvalency, pharmaceutical companies. Investment in new
self-assembling, electrostatic interactions, drugs requires several steps and it is mandato-
chemical stability and low cytotoxicity. These ry to carry out various screening tests before
varied characteristics make dendrimers a good starting the studies in human being. These
choice in the medical field for several medical tests are called pre-clinical and comprise the
applications. In this study, the aim was to con- following fields of study: biopharmaceutical
jugate dendrimers with 177 Lu, to observe the (formulation), in vitro pharmacological studies
in vivo behavior of the labeled compound and and in animals in vivo tests for the evaluation
to measure the elementary changes in tumor of potential clinical efficacy. While in vitro
tissue that could be caused by ionizing radia- tests are used to identify the pharmacological
tion. PAMAM G4 dendrimers conjugated with properties (pharmacodynamics effects) of a
DOTA were labeled with Lu. The radiolabeled new drug, in vivo tests are performed in order
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compound was characterized and its stability to evaluate the safety of new drugs prior to
was evaluated by reverse phase high perfor- any clinical trial with humans. Considering
mance liquid chromatography. Radiolabeling the low cost, easy handling and simplicity
yield was > 98% and stable for 24 hours. Bio- related to the legal implications, the pre-clin-
distribution studies of Lu-DOTA-dendrimers ical tests are usually performed in mice (small
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in C57BL/6 melanoma-bearing mice showed size animal model). There are several mice
blood clearance with hepatic and renal depu- strains developed for the research of new drugs.
ration and tumor uptake. The concentrations The most used strains are C57BL/6J, A/J and
of Br, Ca, Cl, Fe, K, Mg, Na, Rb, S, and Zn were BALB/c. Some of them are inbreed for high
determined in tumor tissues of C57BL/J6 mice and low antibody-producer (H and L ), some
III III
treated with 177 Lu-DOTA dendrimers and in for maximum and minimum inflammatory
untreated mice. The results showed decreased response AIR and AIR , some for autoim-
MAX MIN
concentrations of Br (62%), Ca (24%), Cl (51%), mune diseases (B10.R , NZW and NZB), others
III
K (12%), and Na (60%) and increased concen- are mutants for muscular dystrophy (SJL/J and
trations of Fe (8%), Mg (28%), Rb (100%), S (6%), Dm(dmdx)/J). This study aims to determine
and Zn (4%) in tumor tissues of mice treated the Fe concentration in whole blood of these
with Lu-DOTA-dendrimers. These data may distinct mice strains. The results will be cor-
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Instituto de Pesquisas Energéticas e Nucleares