RESUMO
The aim of present investigation was to evaluate biodistribution in healthy animals and in tumor models of the radiopharmaceuticals (99m)Tc-EDDA/tricine-HYNIC-Lys3-Bombesin (HYNIC-Lys3-BN) and (99m)Tc-NA/tricine-HYNIC-Lys3-BN. Biodistribution and pharmacokinetics were carried out over 24 hours. To do so, 24 healthy Wistar rats were used and were administered 37.0 ± 0.8 MBq/rat of each radiopharmaceutical. For the tumor model study, 20 CD-1 nude mice were used and prostate tumors (PC3) were implanted in all the mice. Ten days later, tumor volumes were calculated and 40.00 ± 0.04 MBq/mice of each radiopharmaceutical were injected. Both showed high radiochemical purity: 98.08 ± 0.25% for EDDA/tricine product and 95.1 ± 0.3% for the conjugate with NA/tricine. Uptake of the radiopharmaceutical with NA/tricine was significantly higher in organs of the reticulo-endothelial system of healthy Wistar rats during 24h, specifically in the liver and spleen. Both labeled compounds showed no significant differences between their blood elimination half lives. Average of tumor growth was 0.93 ± 0.02 cm(3) and affinity for tumors showed a growing and specific binding of both radiopharmaceuticals, although it was significantly higher for the EDDA/tricine conjugate. This outcome made it possible to corroborate the direct relationship between the density of gastrin releasing peptide and its receptors (GRPr) and the variation of the accumulation of the radiopharmaceuticals in the tumor. Use of EDDA/tricine as coligand is more appropriate than NA/tricine for labeling of HYNIC-Lys3-BN with (99m)Tc.
Assuntos
Bombesina/análogos & derivados , Ácido Edético/análogos & derivados , Glicina/análogos & derivados , Niacina/farmacocinética , Compostos de Organotecnécio/farmacocinética , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Animais , Bombesina/sangue , Bombesina/farmacocinética , Linhagem Celular Tumoral/transplante , Ácido Edético/farmacocinética , Peptídeo Liberador de Gastrina/análise , Trato Gastrointestinal/diagnóstico por imagem , Glicina/farmacocinética , Rim/diagnóstico por imagem , Ligantes , Fígado/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Masculino , Camundongos , Camundongos Nus , Compostos de Organotecnécio/sangue , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Cintilografia , Compostos Radiofarmacêuticos/sangue , Compostos Radiofarmacêuticos/farmacocinética , Ratos , Ratos Wistar , Receptores da Bombesina/análise , Baço/diagnóstico por imagem , Distribuição TecidualRESUMO
Bombesin (BN) and its mammalian equivalent, gastrin-releasing peptide (GRP), stimulate cell proliferation and are involved in the pathogenesis of several types of human cancer. BN/GRP and their receptors were shown to be critical for the growth of various human malignancies, such as small-cell lung, prostate, ovary, stomach and breast cancers in the human tumor xenograft model. In the present study, a fast, sensitive, robust method was developed for the determination and quantification of a BN/GRP receptor antagonist RC-3095 (D-Tpi-Gln-Trp-Ala-Val-Gly-His-Leupsi(CH2NH)Leu-NH2), in human plasma by liquid chromatography coupled with tandem mass spectrometry. RC-3095 was extracted from 0.2 ml human plasma by protein precipitation using cold acetonitrile (0.4 ml). The method has a chromatographic run of 10 min using a C(8) analytical column (150 mm x 4.6 mm i.d.) and the linear calibration curve over the range was linear from 20 to 10000 ng ml(-1) (r(2)>0.994). The between-run precision, based on the relative standard deviation replicate quality controls, was 5.7% (60 ng ml(-1)), 7.1% (600 ng ml(-1)) and 6.8% (8000 ng ml(-1)). The between-run accuracy was +/-0.0, 2.1 and 3.1% for the above-mentioned concentrations, respectively. The developed procedure allows the quantitative determination of peptide RC-3095 for pharmacokinetics studies in human plasma.