Abstract
The αvβ3 integrin is an important cell adhesion receptor involved in tumor-induced angiogenesis and tumor metastasis. The high binding specificity to αvβ3 integrins of peptides containing Arg-Gly-Asp (RGD) residue suggests that the radiolabeled RGD peptides be useful as tumor specific imaging agents. Recently, several radionuclides were used to detect αvβ3 integrins and were suitable for noninvasive determination of tumor status, therapy monitoring and possibility of tumor metastasis. Since 99mTc is characteristic of excellent radionuclide with a high-resolution 140.5 keV γ, a half-life 6 h, economically and conveniently available from 99Mo-99mTc generator and extensively used in nuclear medicine, it will be significant to develop 99mTc labeled RGD peptide for clinical use in nuclear medicine. Synthesis of NHS-HYNIC, conjugation of RGD peptide with NHS-HYNIC and preparation of [99mTc(CO)3(OH2)3]+ were carried out respectively according to the previous reports [Abrams et al. J Nucl Med 31(1990) 2022, Su et al. Bioconjugate Chem 13(2002) 561 and Alberto et al. J Am Chem Soc 120(1998) 7987]. RGD peptide was labeled with [99mTc(CO)3(OH2)3]+ via hydrazinonicotinamide as a bifunctional chelator. 99mTc(I)-HYNIC-RGD was prepared by mixing the [99mTc(CO)3(OH2)3]+ solution with HYNIC-RGD in PBS buffer at room temperature. Radiochemical characterization for 99mTc(I)-HYNIC-RGD were conducted by thin layer chromatography, electrophoresis, and HPLC. According to the results, the radiochemical purity for 99mTc(I)- HYNIC-RGD was around 60%. The synthesis and labeling work for 99mTc(I)-HYNIC-RGD has been established in this study. Furthermore in vitro and in vivo tests for 99mTc(I)-HYNIC-RGD for tumor angiogenesis imaging study are underway.