A study on the biological distribution and imaging of ⁹⁹Tc^m-c(RGD)₂ in nude mice bearing different types of tumors

Objective: Using radionuclide ⁹⁹Tc^m labeled the new-developed RGD peptide, namely c(RGD)₂, to study the biological distribution and analyze the tumor imaging in nude mice bearing human glioma U87 cells, human hepatocellular carcinoma HepG2 cells or transplanted human cervical carcinoma Hela cells, in order to investigate the specific early diagnostic prospects of the probe to the tumor with high expression of integrin alpha v beta 3 receptor. Methods: c(RGD)₂ was labeled with ⁹⁹Tc^m by stannous chloride direct labelling method and purified with Sephadex G10. The tumor mouse models bearing U87, HepG2 and Hela xenografts were established. The tumor biological distribution and imaging were studied after injecting the labeled peptide into the tumor models. The differences of ⁹⁹Tc^m-c(RGD)₂ uptake in three kinds of tumor were analyzed. Results: ⁹⁹Tc^m-c(RGD)₂ had relative higher tumor/heart, tumor/spleen, tumor/blood ratios in all three tumor models. The tumor/kidney and tumor/bladder ratios were lower than 1. The increase of the T/NT ratio in the other organs was not obvious. The tumor was identified at 0.5 hour post injection of ⁹⁹Tc^m-c(RGD)₂ and the tumor imaging became clearer with the extension of time to 6 h. In nude mice bearing Hela, tumor imaging was not clear and abdominal viscera showed a dense aggregation. ANOVA was used to analyze the uptake values of ⁹⁹Tc^m-c(RGD)₂ in three kinds of tumors, and the commonly used Bonferroni method was applied to select for further pairwise groups comparison, and the P values were < 0.05. Conclusion: ⁹⁹Tc^m-c(RGD)₂ is mainly excreted by urinary system, and the blood scavenging rate is fast, and the intake for the important organs such as heart and liver is low. The probe showed targeted and high-quality imaging characteristics for both U87 and HepG2 tumors, and had better biological distribution and imaging results for glioma U87. However, the results in Hela cells were unsatisfactory. (authors)