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
Carregando...
Data
Data de publicação:
2005
Orientador
Título da Revista
ISSN da Revista
Título do Volume
É parte de
É parte de
É parte de
É parte de
INTERNATIONAL NUCLEAR ATLANTIC CONFERENCE; ENCONTRO NACIONAL DE APLICACOES NUCLEARES, 7th
Exportar
Resumo
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.
Como referenciar
SUZUKI, M.F.; SILVA, M.A.; CALDEIRA FILHO, J.S.C.; 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. In: INTERNATIONAL NUCLEAR ATLANTIC CONFERENCE; ENCONTRO NACIONAL DE APLICACOES NUCLEARES, 7th, ago. 28 - set. 2, 2005, Santos, SP. Anais... Disponível em: http://repositorio.ipen.br/handle/123456789/18254. Acesso em: 13 Feb 2025.
Esta referência é gerada automaticamente de acordo com as normas do estilo IPEN/SP (ABNT NBR 6023) e recomenda-se uma verificação final e ajustes caso necessário.