Direct Intratumoral Injection ¹⁸⁸Re-Doped SPIO for Treatment of HT-1080 Tumor Xenografts Mouse Model

Objectives: To evaluate the value of ¹⁸⁸Re-doped SPIO (Superparamgnetic Iron Oxide) for treatment of HT-1080 tumor xenografts mouse model. Methods The ¹⁸⁸Re-doped SPIO Nanoparticle was obtained by classical coprecipitation in deoxygenated water and its size determined by transmission electron microscope. The mice treated with ¹⁸⁸Re-SPIO were put into four random sub-groups and received ¹⁸⁸Re activity equivalent to 2.96 (group 1, n = 5), 5.55 (group 2, n = 5), 8.14 (group 3, n = 5) and 14.8 MBq (group 4, n = 5), respectively. Group 5 received 100 μl of ¹⁸⁸Re perrhenate solution equivalent to 3.3 MBq (n = 5). Group 6 received “cold” SPIO (n = 5). After treatment, the mice from groups 4 and 5 were maintained in metabolism cages for 72 h and were fed ad libitum. Urine and faeces were collected every 12 h and measured with a gamma counter to evaluate ¹⁸⁸Re elimination. Irradiation doses delivered to tumors were estimated. The tumor volume (V) and mice weight were measured twice weekly. Laboratory testing of red and white blood cells and platelets, liver function, renal function were performed shortly before treatment, on the third day, and at 1, 2 and 6 wk after injection. Toxicities to vital organs, such as kidney, heart, liver, lung and spleen were evaluated by pathologic examination after completion of the therapy study. The mean tumor growth inhibition rate (MGI) was calculated according to the volume of the tumor. The survival ratio of mice was also monitored every day. Mice were imaged with SPECT equipped with a pinhole collimator 1, 4, 24, 48 and 72 h after the administration. Results The prepared ¹⁸⁸Re-doped SPIO suspending in DI water was rather stable. The particle diameter of ¹⁸⁸Re-doped SPIO was 10-20 nm. Irradiation dose delivered to tumors were estimated, group 1 @ 8 Gy, group 2 @ 15 Gy, group 3 @ 22 Gy, group 4 @ 40 Gy, Group 5 @ 9Gy, respectively. For therapeutic efficacy, inhibition of tumor growth in mice treated with ¹⁸⁸Re-doped SPIO was precisely controlled [mean tumor growth inhibition rate (MGI) = 0.065] and had longer survival time [life-span (LS) = 88.36%]. No ¹⁸⁸Re elimination and no toxicity to vital organs were detected. Conclusions The study pointed the benefits of the ¹⁸⁸Re-doped SPIO radiotherapeutics for cancer treatment by direct intratumoral injection.