JOSE DE SOUZA CALDEIRA FILHO

JOSE DE SOUZA CALDEIRA FILHO

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Development of somatostatin based radiopharmaceuticals for receptor mediated radionuclide therapy
2007 - ARAUJO, E.B.; CALDEIRA FILHO, J.S.; NAGAMATI, L.T.; MURAMOTO, E.; COLTURATO, M.T.; COUTO, R.; OKASAKI, K.; SUZUKI, M.F.; GUIMARAES, M.I.C.C.
The paper describes the methodology used for and the results of labelling [Tyr3 ]octreotate (TATE) with radioiodine (131I) and [DOTA,Tyr3 ]octreotate (DOTATATE) with 131I and lutetium (177Lu). The quality control and purification procedures are also described. Biodistribution studies were performed in normal Swiss mice and in nude mice bearing AR42J tumours. In vitro studies were used to evaluate the affinity of the radiopharmaceuticals for somatostatin receptors in rat brain cortex and tumour cells. Saturation binding and the internalization of the labelled peptides were determined. The frequency of micronuclei in peripheral blood lymphocytes exposed to different radioactive concentrations of [131I]DOTATATE and [ 177Lu]DOTATATE was evaluated by micronucleus assay.
Induction of micronucleus by [DOTA, Tyr3]octreotate labeled with sup(131)I and sup(177)Lu in peripheral blood lymphocytes IN VITRO
2004 - SUZUKI, M.F.; SILVA, M.A.; CALDEIRA, J.S.; COLTURATO, M.T.; ARAUJO, E.B.; BARTOLINI, P.; OKAZAKI, K.
Genotoxic evaluation of [DOTA,Tyrsup(3)]octreotate labeled with sup(131)I and sup(177)Lu in human peripheral lymphocytes in vitro by micronucleus assay
2005 - SUZUKI, M.F.; SILVA, M.A.; CALDEIRA FILHO, J.S.C.; COLTURATO, M.T.; ARAUJO, E.B.; BARTOLINI, P.; OKAZAKI, K.
The radiolabeled receptor-binding peptides have being used for cancer diagnosis and therapy. The octreotate, a somatostatin analogue peptide, bound to various tumors expressing sst receptors (thyroid, pancreas, prostrate, melanoma and lymphomas). The amount and the type of receptors for somatostatin influence the tissue uptake. The [DOTA, Tyr3 ]octreotate has been used because of its high affinity to somatostatin subtype receptors sstr2 and sstr5. The pharmacokinetic study showed that the blood clearance is rapid and only 9% of the intravenous injected activity remains in human blood after one hour. The aim of this study was to evaluate the cytogenetic effect of radiolabeled [DOTA, Tyr3 ]octreotate in blood cells in vitro, using the cytokinesis-block micronucleus (MN) assay. This technique allows evaluating the mutagenic effects of both endogenous and exogenous agents at chromosome level. Blood samples of healthy donors were collected in heparinized syringes and exposed to different activities of [DOTA, Tyr3 ]octreotate labeled with with 131I (n=3) and 177Lu (n=3), where radioactive concentration ranged from 600 to 5600 kBq/mL, corresponding to an injected activity of 3.1 to 28.9 GBq in a reference man of 70 kg weight. 131I and 177Lu are beta- and gamma-emitters. After one-hour exposition to radiopharmaceuticals at 37o C, the cells were washed with culture medium for removing the non internalised octreotate and cultivated for 72 hours, according to criteria adopted by the IAEA. The results showed a positive correlation between radioactive concentrations (X) and the frequency of binucleated cells with micronuclei (Y) (P<0.05). The model for the best fit of data was the linear one (Y = a + bX). The equation for [131I-DOTA, Tyr3 ]octreotate was Y = (1.634 ± 0.236) + (0.912 ± 0.137) 10-3 X and for [177Lu-DOTA, Tyr3 ]octreotate was Y = (1.715 ± 0.342) + (0.743 ± 0.135) 10-3 X. The non labeled molecule, [DOTA, Tyr3 ]octreotate, has no influence in the induction of cytogenetic damage. The micronucleus assay with rat pancreatic tumor cells (AR42J) that express the sstr2 receptor for somatostatin, submitted to these radiopharmaceuticals, are in course.
Genotoxic evaluation of [DOTA, Tyrsup(3)]octreotate labelled with sup(131)I and sup(177)Lu in human peripheral lymphocytes in vitro by micronucleus assay
2007 - SUZUKI, MIRIAM F.; SILVA, MARCIA A. da; CALDEIRA FILHO, JOSE de S.; COLTURATO, MARIA T.; ARAUJO, ELAINE B. de; BARTOLINI, PAOLO; OKAZAKI, KAYO
[DOTA, Tyr3 ]octreotate has been used for cancer diagnosis and therapy because of its high affinity to somatostatin subtype receptors sstr2 and sstr5. The aim of this study was to evaluate the cytogenetic effect of radio-labelled [DOTA, Tyr3 ]octreotate in blood cells in vitro, using the cytokinesis-block micronucleus assay. Blood samples of healthy donors were exposed to different activities of [DOTA, Tyr3 ]octreotate labelled with 131I (n = 3) and 177Lu (n = 3), where radioactive concentration ranged from 600 to 5600 kBq/mL. The cells were cultivated according to criteria adopted by the IAEA (Vienna). The results showed a positive correlation between radioactive concentrations (X) and the frequency of binucleated cells with micronuclei (Y) (P < 0.05). The linear equations were similar: for the 131I labelled, Y = (1.634 ± 0.236) + (0.912 ± 0.137) 10–3 X and for the 177Lu labelled, Y = (1.715 ± 0.342) + (0.743 ± 0.135) 10–3 X.