Design, preparation, in vitro and in vivo evaluation of (99m)Tc-N2S2-Tat(49-57)-bombesin: a target-specific hybrid radiopharmaceutical.
Int J Pharm
; 375(1-2): 75-83, 2009 Jun 22.
Article
em En
| MEDLINE
| ID: mdl-19393305
The gastrin-releasing peptide receptor (GRP-r) is over-expressed in various human tumors. Recently, (99m)Tc-EDDA/HYNIC-Lys(3)-bombesin ((99m)Tc-BN) was reported as a radiopharmaceutical with specific cell GRP-r binding and images in breast cancer patients demonstrated distinct radioactivity accumulation in malignant tissue. The HIV Tat-derived peptide has been used to deliver a large variety of cargoes into cells. Therefore, a new hybrid radiopharmaceutical of type (99m)Tc-N(2)S(2)-Tat(49-57)-Lys(3)-bombesin ((99m)Tc-Tat-BN) would increase cell uptake. The aim of this research was to prepare and assess in vitro and in vivo uptake kinetics in cancer cells of (99m)Tc-Tat-BN and to compare its cellular internalization with that of (99m)Tc-BN. Structures of N(2)S(2)-Tat-BN and Tc(O)N(2)S(2)-Tat-BN were calculated by an MM procedure. (99m)Tc-Tat-BN was synthesized and stability studies carried out by HPLC and ITLC-SG analyses in serum and cysteine solutions. In vitro internalization was tested using human prostate cancer PC-3 cells and breast carcinoma cell lines MDA-MB231 and MCF7. Biodistribution was determined in PC-3 tumor-bearing nude mice. Results showed a minimum energy of 271 kcal/mol for N(2)S(2)-Tat-BN and 300 kcal/mol for Tc(O)N(2)S(2)-Tat-BN. (99m)Tc-Tat-BN radiochemical purity was >90%. In vitro studies demonstrated stability in serum and cysteine solutions, specific cell receptor binding and internalization in three cell lines was significantly higher than that of (99m)Tc-BN (p<0.05). The tumor-to-muscle radioactivity ratio was 8.5 for (99m)Tc-Tat-BN and 7 for (99m)Tc-BN. Therefore, this hybrid is potentially useful in breast and prostate cancer imaging.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bombesina
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Compostos de Organotecnécio
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Sistemas de Liberação de Medicamentos
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Compostos Radiofarmacêuticos
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Int J Pharm
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
México
País de publicação:
Holanda