Preparação e padronização de metodologia de marcação in vitroe estudo de biodistribuição do octreotídeo-[Tyr3]-HYNIC/EDDA/TRICINA-[99mTc / PREPARATION AND STANDARDIZATION OF AN IN VITRO LABELING METHODOLOGY AND STUDY OF [99mTc]-EDDA/TRICINE/HYNIC-[Tyr3]-OCTREOTIDE BIODISTRIBUTION

AUTOR(ES)
DATA DE PUBLICAÇÃO

2008

RESUMO

Somatostatine receptors are widely expressed by several tumors, especially of the neuroendocrine origin. In vivo images of these tumors using radiolabeled somatostatine analogues became a useful clinical tool in oncology. The radiopharmaceutical currently applied is [111In-DTPA-Phe1-D]-octreotide. However, the use of indium-111 (111In) is limited by the production in cyclotron as well as the long physical half-life and high gamma energy, resulting in high dose of radiation to the patient and suboptimal characteristics of image. The technetium-99m (99mTc), produced by a radioisotope generator and daily viability, with half-life of six hours and gamma rays emission of 140 keV, is ideal for imaging procedures in nuclear medicine. The objective of this work was the development of a technetium-99m radiopharmaceutical based on a peptide somatostatine derivatived, the octreotide, to be applied in the diagnosis of neuroendocrine tumors in nuclear medicine. The labeling by indirect method was based in the addition of 20 g of the peptide TOC-HYNIC (octreotide-[Tyr3]-HYNIC), 10 mg of EDDA and 20 mg of tricine coligands, approximately 1110 MBq (30 mCi) of sodium pertecnetate and 15 g of the reducing agent SnCl2.2H2O in final pH 6.5, followed by the incubation for 10 minutes in water boiling bath. The radiochemical purity was determined 30 minutes and 5 hours after labeling by thin layer chromatography, using as mobile phase methanol:ammonium acetate (1:1), methilethilketone and sodium citrate buffer 0.1 N pH 5.0, and as stationary phases the silica gel plates (TLC-SG and ITLC-SG). This labeling referred as standard condition resulted in radiochemical purity of 89.91 4.82 % at 30 minutes and 91.37 6.14 % at 5 hours. Studying the labeling parameters: mass of the coligands, reducing agent and peptide, time and temperature of reaction, pH and activity, the best results obtained were 92.14 0.30 % at 30 minutes and 90.60 0.35 % at 5 hours using 80 g octreotide-HYNIC, 10 mg of EDDA, 20 mg of tricine, 150 g of SnCl2.2H2O in a final pH 8.0, and activity up to 3700 MBq (100 mCi). This formulation can be an alternative for the administration of more than one patient per labeling procedure, using a lyophilized reagent. The biodistribution performed by invasive method in the intervals of 1.5 and 4 hours after intravenous administration of the radiopharmaceutical in Swiss mice determined the percentage of the activity administered in the blood and the various organs. The biodistribution data in Swiss and Nude mice bearing AR42J tumor (rat pancreatic adenocarcinoma) were compatible with the distribution of the labeled peptide: fast blood clearance, high uptake in the kidneys due to the elimination by the urinary tract, and high uptake in organs with high density of somatostatine receptors like lung, stomach, pancreas and tumor in the case of Nude mice. The uptake of the radiolabeled peptide in the abdominal region was not significant and represents an advantage related to the diagnosis of neuroendocrine tumors, frequently found in this region. The labeling and biodistribution results described in this study showed the potential of the 99mTc-labeled peptide to be applied in diagnostic procedures in nuclear medicine.

ASSUNTO(S)

tecnécio-99m octreotídeo tumor neuroendócrino octreotídeo tumor neuroendócrino tecnécio-99m

ACESSO AO ARTIGO

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