RESUMO
Glioblastoma is considered the most common malignant primary tumor of central nervous system. In spite of the current standard and multimodal treatment, the prognosis of glioblastoma is poor. For this reason, new therapeutic approaches need to be developed to improve the survival time of the glioblastoma patient. In this study, we performed a preclinical experiment to evaluate therapeutic efficacy of 166Ho microparticle suspension administered by microbrachytherapy on a minipig glioblastoma model. Twelve minipigs were divided in 3 groups. Minipigs had injections into the tumor, containing microparticle suspensions of either 166Ho (group 1; n = 6) or 165Ho (group 2; n = 3) and control group (group 3; n = 3). The survival time from treatment to euthanasia was 66 days with a good state of health of all minipigs in group 1. The median survival time from treatment to tumor related death were 8.6 and 7.3 days in groups 2 and control, respectively. Statistically, the prolonged life of group 1 was significantly different from the two other groups (p < 0.01), and no significant difference was observed between group 2 and control (p=0.09). Our trial on the therapeutic effect of the 166Ho microparticle demonstrated an excellent efficacy in tumor control. The histological and immunohistochemical analysis showed that the efficacy was related to a severe 166Ho induced necrosis combined with an immune response due to the presence of the radioactive microparticles inside the tumors. The absence of reflux following the injections confirms the safety of the injection device.
RESUMO
Alpha-particle-emitting radionuclides have been the subject of considerable investigation as cancer therapeutics, since they have the advantages of high potency and specificity. Among α-emitting radionuclides that are medically relevant and currently available, the lead-212/bismuth-212 radionuclide pair could constitute an in vivo generator. Considering its short half-life (T1/2 = 60.6 min), 212Bi can only be delivered using labelled carrier molecules that would rapidly accumulate in the target tumor. To expand the range of applications, an interesting method is to use its longer half-life parent 212Pb (T1/2 = 10.6 h) that decays to 212Bi. The challenge consists in keeping 212Bi bound to the vector after the 212Pb decay. Preclinical and clinical studies have shown that a variety of vectors may be used to target alpha-emitting radionuclides to cancer cells. Nanoparticles, notably liposomes, allow combined targeting options, achieving high specific activities, easier combination of imaging and therapy and development of multimodality therapeutic agents (e.g., radionuclide therapy plus chemotherapy). The aim of this work consists in assessing the in vitro stability of 212Pb/212Bi encapsulation in the liposomes. Indeed, the release of the radionuclide from the carrier molecules might causes toxicity to normal tissues. To reach this goal, Asymmetrical Flow Field-Flow Fractionation (AF4) coupled with a Multi-Angle Light Scattering detector (MALS) was used and coupling with a gamma (γ) ray detector was developed. AF4-MALS-γ was shown to be a powerful tool for monitoring the liposome size together with the incorporation of the high energy alpha emitter. This was successfully extended to assess the stability of 212Bi-radiolabelled liposomes in serum showing that more than 85% of 212Pb/212Bi is retained after 24 h of incubation at 37 °C.
