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 In-111/Lu-177-(oxine)(3) to afford In-111/Lu-177-liposome. The stability of In-111/Lu-177-liposome in serum was investigated. The biodistribution, scintigraphic imaging and pharmacokinetics of In-111/Lu-177-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 In-111/Lu-177 into liposomes was 95%. After incubation at 37 degrees C for 72h in serum, more than 83% of radioactivity was still retained in the intact In-111/Lu-177-liposomes. The biodistribution of In-111-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 72h 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 Lu-177-liposomes. Scintigraphic imaging with In-111-liposomes showed unambiguous tumor images at 48 It p.i. Dose estimation showed that the absorbed dose in tumor from Lu-177-fposornes was 5.74 x 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. (c) 2006 Elsevier B.V. All rights reserved.