Imaging and biodistribution of ⁹⁹Tc^m labeled cyclic RGD peptide in nude mice with xenografted lung adenocarcinoma

Objective: To synthesize ⁹⁹Tc^m labeled hydrazine-nicotinamide (HYNIC)-c (RGDfK) and evaluate its biodistribution and imaging in the severe combined immunodeficiency (SCID) nude mice bearing human lung adenocarcinoma. Methods: (1) ⁹⁹Tc^m-HYNIC-c(RGDfK) was prepared by a two-step method using tricine and ethylenediamine diacetate (EDDA) as coligands and HYNIC as the dual functional chelator. The bioactivity of ⁹⁹Tc^m-HYNIC-c (RGDfK) was measured by cell binding experiments. (2) The nude mice bearing human A549 lung adenocarcinoma were randomly divided into 7 groups with 5 in each group. The 7th group was the competitive inhibition control group and was administrated 100 μg HYNIC-c (RDGfK) 30 min earlier before the injection of ⁹⁹Tc^m-HYNIC-c (RGDfK). The nude mice were scanned at 0.5, 1, 2, 4, 8 and 12 h respectively after intravenous injection of 7.4 MBq ⁹⁹Tc^m-HYNIC-c (RGDfK). The biodistribution of the agent was measured as % ID/g. The uptake ratio of tumor to muscle (T/NT) was also measured by placing ROI on ⁹⁹Tc^m-HYNIC-c (RGDfK) SPECT imaging. (3) Gamma imaging was performed in 6 mice including 3 in the competitive inhibition control group at 0.5, 1, 2, 4, 8 and 12 h post injection. Results: The labeling yield of ⁹⁹Tc^m-HYNIC-c (RGDfK) was more than 90%, and the radiochemical purity was more than 95%. ⁹⁹Tc^m-HYNIC-c (RGDfK) can specifically bind with A549 adenocarcinoma cells with a binding rate up to 36.14%. Biodistribution study showed that the uptake in the kidney was above 20 % ID/g during 0.5-8 h post injection. The % ID/g in tumor was 10.52 ± 1.48 at 0.5 h, 17.26 ±2.81 at 8 h, and 8.93 ±0.90 at 12 h. However, the % ID/g in tumor was only 2.29 ±0.85 in the competitive inhibition control group at 0.5 h. The highest T/NT was 6.87 at 8 h by the ROI analysis. Xenografted tumors could be visualized at 1 h and delineated more clearly from 4 to 8 h post injection of ⁹⁹Tc^m-HYNIC-c (RGDfK). Conclusions: ⁹⁹Tc^m-HYNIC-c (RGDfK) can be readily synthesized. Its binding with A549 lung adenocarcinoma cells is specific and the binding rate is high. (authors)