Evaluation of 188Re-labeled PEGylated nanoliposome as a radionuclide therapeutic agent in an orthotopic glioma-bearing rat model

Abstract

Purpose In this study, the 188 Re-labeled PEGylated nanoliposome ( 188 Re-liposome) was prepared and evaluated as a therapeutic agent for glioma. Materials and methods The reporter cell line, F98 luc was prepared via Lentivector expression kit system and used to set up the orthotopic glioma-bearing rat model for non-invasive bioluminescent imaging. The maximum tolerated dose applicable in Fischer344 rats was explored via body weight monitoring of the rats after single intravenous injection of 188 Re-liposome with varying dosages before the treatment study. The OLINDA/EXM 1.1 software was utilized for estimating the radiation dosimetry. To assess the therapeutic efficacy, tumor-bearing rats were intravenously administered 188 Re-liposome or normal saline followed by monitoring of the tumor growth and animal survival time. In addition, the histopathological examinations of tumors were conducted on the 188 Re-liposome-treated rats. Results By using bioluminescent imaging, the well-established reporter cell line (F98 luc ) showed a high relationship between cell number and its bioluminescent intensity ( R 2 =0.99) in vitro; furthermore, it could also provide clear tumor imaging for monitoring tumor growth in vivo. The maximum tolerated dose of 188 Re-liposome in Fischer344 rats was estimated to be 333 MBq. According to the dosimetry results, higher equivalent doses were observed in spleen and kidneys while very less were in normal brain, red marrow, and thyroid. For therapeutic efficacy study, the progression of tumor growth in terms of tumor volume and/or tumor weight was significantly slower for the 188 Re-liposome-treated group than the control group ( P <0.05). As a result, the lifespan of glioma-bearing rats treated with 188 Re-liposome was prolonged 10.67% compared to the control group. Conclusion The radiotherapeutic evaluation by dosimetry and survival studies have demonstrated that passive targeting 188 Re-liposome via systemic administration can significantly prolong the lifespan of orthotopic glioma-bearing rats while maintaining reasonable systemic radiation safety. Therefore, 188 Re-liposome could be a potential therapeutic agent for glioblastoma multiforme treatment.

Getting into the brain: liposome-based strategies for effective drug delivery across the blood&ndash;brain barrier

“…294 In this way, recent studies suggest that brachytherapy with liposomally encapsulated 186 Re or 188 Re isotopes holds significant promise for glioma therapy. 229,242,245 These studies demonstrated that animals treated with 186 Re or 188 Re liposomes had significantly prolonged survival, independent of the route of administration. 229,242 Also, 188 Re liposomes have been explored for diagnostic evaluation, revealing the potential of these liposomes as a future theranostic agent for brain gliomas.…”

“…229,242,245 These studies demonstrated that animals treated with 186 Re or 188 Re liposomes had significantly prolonged survival, independent of the route of administration. 229,242 Also, 188 Re liposomes have been explored for diagnostic evaluation, revealing the potential of these liposomes as a future theranostic agent for brain gliomas. 245 A wide variety of liposome-encapsulated anticancer drugs have also been developed for both experimental and clinical oncology.…”

In vitro and in vivo inhibition of tumor cell viability by combined dihydroartemisinin and doxorubicin treatment, and the underlying mechanism

“…Dihydroartemisinin (DHA) is an active derivative of the first-line anti-malarial drug artemisinin, which has been extracted from the goldenrod Artemisia annua in China for the first time (5,6). Due to the quick activity, effectiveness and safety of artemisinin and its derivative, the World Health Organization promotes their application in the treatment of severe and drug-resistant malaria (7).…”

miR-101 inhibits glioma cell invasion via the downregulation of COX-2

“…High morbidity and mortality rates make glioma the fourth most fatal malignant cancer ( 3 ). Currently, the standard treatment for glioma is surgical resection followed by combined administration of radiation and adjuvant chemotherapy ( 4 , 5 ). Despite current therapeutic efforts, the median survival time (~14 months) has not changed significantly in the past decades ( 6 ).…”