Preliminary Studies of 177 Lu-Diethylenetriamine Penta-Acetic Acid-Deoxyglucose in Hepatic Tumor-Bearing Mice

Abstract

Objective:

The purpose of this study was to explore the potential use of ¹⁷⁷Lu-diethylenetriamine penta-acetic acid-deoxyglucose (¹⁷⁷Lu-DTPA-DG) as a radiopharmaceutical for hepatic tumor treatment.

Methods:

Lutetium-177 (¹⁷⁷Lu) was labeled with DTPA-DG by adding 2 mCi ¹⁷⁷LuCl₃ to 0.05 mg DTPA-DG (pH 5–6) at room temperature for 1 h. The quality of the¹⁷⁷Lu-DTPA-DG solutions was determined by thin-layer chromatography and high-performance liquid chromatography. Cellular uptake studies with ¹⁸F-fluorodeoxyglucose (FDG), ¹⁷⁷Lu-DTPA-DG and ¹⁷⁷Lu-DTPA and a blocking study with 1.0 mg d-glucose were performed. Biodistribution, imaging, and radiotherapy studies of ¹⁷⁷Lu-DTPA-DG were performed with the SMMC-7721 model.

Results:

¹⁷⁷Lu-DTPA-DG had a high radiochemical purity (>97%). The cellular uptake of ¹⁷⁷Lu-DTPA-DG was much higher than that of the ¹⁷⁷Lu-DTPA. The biodistribution of ¹⁷⁷Lu-DTPA-DG demonstrated that the complex accumulated in the tumor with high tumor/blood and tumor/muscle ratios. The tumors in mice in the ¹⁷⁷Lu-DTPA-DG group clearly displayed the high uptake of ¹⁷⁷Lu-DTPA-DG. After radiotherapy with ¹⁷⁷Lu-DTPA-DG, tumor growth decreased, and the overall survival was longer than that in the ¹⁷⁷LuCl₃ group (268.58 ± 17.96 mm³ vs. 507.43 ± 55.72 mm³, p = 0.002) and the normal saline group (268.58 ± 17.96 mm³ vs. 483.68 ± 27.51 mm³, p < 0.05).

Conclusions:

This preliminary study suggests that ¹⁷⁷Lu-DTPA-DG has the potential to become a liver radiopharmaceutical agent and should be further investigated.