Internal radiotherapy and dosimetric study for ¹¹¹In/¹⁷⁷Lu-pegylated liposomes conjugates in tumor-bearing mice

In vivo characterization and dosimetric analysis has been performed to evaluate the potential of pegylated liposomes as carriers of radionuclides in tumor internal radiotherapy. Methods: The DTPA/PEG-liposomes were synthesized with a medium size of 110 nm, conjugated with ¹¹¹In/¹⁷⁷Lu-(oxine)₃ to afford ¹¹¹In/¹⁷⁷Lu-liposome. The stability of ¹¹¹In/¹⁷⁷Lu-liposome in serum was investigated. The biodistribution, scintigraphic imaging and pharmacokinetics of ¹¹¹In/¹⁷⁷Lu-liposomes after intravenous(i.v.) injection into C-26 tumor-bearing BALB/cByJ mice were studied. Radiation dose was estimated by MIRD-III program. Results: The incorporation efficiency of ¹¹¹In/¹⁷⁷Lu into liposomes was 95%. After incubation at 37 °C for 72 h in serum, more than 83% of radioactivity was still retained in the intact ¹¹¹In/¹⁷⁷Lu-liposomes. The biodistribution of ¹¹¹In-liposomes showed that the radioactivity in the blood decreased from 23.14±8.16%ID/g at 1 h to 0.02±0.00%ID/g at 72 h post-injection (p.i.), while reaching its maximum accumulation in tumors at 48 h p.i., with half-life in blood of 10.2 h. The results were supported by that of ¹⁷⁷Lu-liposomes. Scintigraphic imaging with ¹¹¹In-liposomes showed unambiguous tumor images at 48 h p.i. Dose estimation showed that the absorbed dose in tumor from ¹⁷⁷Lu-liposomes was 5.74×10^-5 Gy/MBq. Conclusions: This study provides an in vivo characterization and dosimetric evaluation for the use of liposome systems as carriers in targeted radionuclide therapy. The results suggest that adequate tumor targeting as well as dose delivered to tumors could be achieved by the use of radionuclide targeted liposomes.