Evaluation of (188)Re-labeled PEGylated nanoliposome as a radionuclide therapeutic agent in an orthotopic glioma-bearing rat model (original) (raw)
Related papers
Neuro-Oncology
A phase I/IIa dose escalation trial was initiated to determine the safety and recommended phase II dose (RP2D) of 186RNL in patients with recurrent glioma. Liposomal rhenium-186 (186RNL) is a source of high energy beta particles and gamma photons with attractive properties for brain CED.Patients with biopsy proven recurrent glioma had computerized treatment planning and placement of up to 4 intracranial catheter(s). Each patient received a single administration of 186RNL by CED. Whole body planar and SPECT/CT imaging from days 1-8 following treatment was performed. Patients were followed for safety, sufficiency of delivery and overall survival. Twenty-one patients across 6 dose escalation cohorts received 1.0-22.3mCi in a volume of 0.6-8.8mL. Mean tumor volume was 8.3mL, patients were heavily pretreated (mean 1.7 recurrences) with poor prognostic factors. There were no CED failures. Mean absorbed radiation dose to the tumor (MARDT) was 271Gy. No dose limiting toxicities were observe...
Multimodal targeting of glioma with functionalized nanoparticles
Cancer Cell International
The most common and aggressive primitive intracranial tumor of the central nervous system is the glioma. The blood–brain barrier (BBB) has proven to be a significant obstacle to the effective treatment of glioma. To effectively treat glioma, different ways have been used to cross the BBB to deliver drugs to the brain. Drug delivery through nanocarriers proves to be an effective and non-invasive technique for the treatment of glioma and has great potential in the treatment of glioma. In this review, we will provide an overview of nanocarrier-mediated drug delivery and related glioma therapy. Nanocarrier-mediated drug delivery techniques to cross the BBB (liposomes, micelles, inorganic systems, polymeric nanoparticles, nanogel system, and biomimetic nanoparticles) are explored. Finally, the use of nanotherapeutic approaches in the treatment of glioblastoma including chemotherapy, radiotherapy, photothermal therapy, gene therapy, glioma genome editing, immunotherapy, chimeric antigen r...
2011
The 188 Re-labeled pegylated nanoliposome (abbreviated as 188 Re-Liposome) was prepared and evaluated for its potential as a theragnostic agent for glioma. 188 Re-BMEDA complex was loaded into the pegylated liposome core with pH 5.5 ammonium sulfate gradient to produce 188 Re-Liposome. Orthotopic Fischer344/F98 glioma tumor-bearing rats were prepared and intravenously injected with 188 Re-Liposome. Biodistribution, pharmacokinetic study, autoradiography (ARG), histopathology, and nano-SPECT/CT imaging were conducted for the animal model. The result showed that 188 Re-Liposome accumulated in the brain tumor of the animal model from 0.28%-0.09% injected dose (ID)/g (n = 3) at 1 hour to a maximum of 1.95%-0.35% ID/g (n = 3) at 24 hours postinjection. The tumor-to-normal brain uptake ratio (T/N ratio) increased from 3.5 at 1 hour to 32.5 at 24 hours. Both ARG and histopathological images clearly showed corresponding tumor regions with high T/N ratios. Nano-SPECT/CT detected a very clear tumor image from 4 hours till 48 hours. This study reveals the potential of 188 Re-Liposome as a theragnostic agent for brain glioma.
Nanoparticle based strategies for the treatment of Glioblastoma
2014
Glioblastoma is the most common and most biologically aggressive primary brain tumour in adults. In spite of tremendous investment into research which has led to the development and application of novel diagnostic and therapeutic measures in the management of glioblastoma, the prognosis is still dismal with median survival time of about 12 – 15 months. Also, the success of most cytotoxic drugs clinically employed in the treatment of glioblastoma is greatly limited by their dose-limiting toxicity which typically manifests as clinically significant reduction in blood cell counts. The aim of this study is to demonstrate that a high dose nanoparticle formulation of the cytotoxic drug lomustine using a self-assembling chitosan amphiphile, quaternary ammonium palmitoyl glycol chitosan would lead to improved survival outcomes without a commensurate increase in toxic effects. The novel nanoparticle based lomustine formulation employed in this study enabled the administration of a lomustine ...
Biomaterials, 2011
To date, glioblastoma treatments have only been palliative. In this context, locoregional drug delivery strategies, which allow for bloodebrain barrier bypass and reduced systemic toxicity, are of major significance. Recent progress in nanotechnology has led to the development of colloidal carriers of radiopharmaceutics, such as lipid nanocapsules loaded with rhenium-188 (LNC 188 Re-SSS) that are implanted in the brain. In our study, we demonstrated that fractionated internal radiation using LNC 188 Re-SSS triggered remarkable survival responses in a rat orthotopic glioma model (cure rates of 83%). We also highlighted the importance of the radioactivity activity gradient obtained by combining a simple stereotactic injection (SI) with convection-enhanced delivery (CED).We assumed that the immune system played a role in the treatment's efficacy on account of the overproduction of peripheral cytokines, recruitment of immune cells to the tumor site, and memory response in long-term survivor animals. Hence, nanovectorized internal radiation therapy with activity gradients stimulating immune responses may represent a new and interesting alternative for the treatment of solid tumors such as glioblastomas.
Drug Delivery Nanosystems for the Localized Treatment of Glioblastoma Multiforme
Materials (Basel, Switzerland), 2018
Glioblastoma multiforme is one of the most prevalent and malignant forms of central nervous system tumors. The treatment of glioblastoma remains a great challenge due to its location in the intracranial space and the presence of the blood⁻brain tumor barrier. There is an urgent need to develop novel therapy approaches for this tumor, to improve the clinical outcomes, and to reduce the rate of recurrence and adverse effects associated with present options. The formulation of therapeutic agents in nanostructures is one of the most promising approaches to treat glioblastoma due to the increased availability at the target site, and the possibility to co-deliver a range of drugs and diagnostic agents. Moreover, the local administration of nanostructures presents significant additional advantages, since it overcomes blood⁻brain barrier penetration issues to reach higher concentrations of therapeutic agents in the tumor area with minimal side effects. In this paper, we aim to review the at...
RADT-24. High Absorbed Doses of RHENIUM-186 Nanoliposomes (RNL) in Recurrent GBM: A Phase 1 Study
Neuro-Oncology, 2020
INTRODUCTION While external beam radiation therapy (EBRT) remains a central component of the management of primary brain tumors, it is limited by tolerance of the surrounding normal brain tissue. Nanoliposomal BMEDA-chelated-186Rhenium (RNL™) permits the delivery of beta-emitting radiation of high specific activity with excellent retention in the tumor. We report on the phase 1 results in recurrent glioma. METHODS A phase 1 dose-escalation study of RNL in recurrent glioma utilizing a standard 3 + 3 design was undertaken to determine the maximum tolerated dose of RNL following stereotactic biopsy. RNL is administered with the BrainLab Flexible Catheter by convection enhanced delivery (CED) with placement guided using iPlan Flow and the Varioguide system. Infusion is followed under whole body planar imaging and SPECT/CT. Repeat SPECT/CT imaging is performed immediately following, and at 1, 3, 5, and 8 days after RNL infustion to obtain dosimetry and distribution. RESULTS Thirteen pati...
Theranostic nanoparticles enhance the response of glioblastomas to radiation
Nanotheranostics
Despite considerable progress with our understanding of glioblastoma multiforme (GBM) and the precise delivery of radiotherapy, the prognosis for GBM patients is still unfavorable with tumor recurrence due to radioresistance being a major concern. We recently developed a cross-linked iron oxide nanoparticle conjugated to azademethylcolchicine (CLIO-ICT) to target and eradicate a subpopulation of quiescent cells, glioblastoma initiating cells (GICs), which could be a reason for radioresistance and tumor relapse. The purpose of our study was to investigate if CLIO-ICT has an additive therapeutic effect to enhance the response of GBMs to ionizing radiation. Methods: NSG mice bearing human GBMs and C57BL/6J mice bearing murine GBMs received CLIO-ICT, radiation, or combination treatment. The mice underwent pre-and post-treatment magnetic resonance imaging (MRI) scans, bioluminescence imaging (BLI), and histological analysis. Tumor nanoparticle enhancement, tumor flux, microvessel density, GIC, and apoptosis markers were compared between different groups using a one-way ANOVA and two-tailed Mann-Whitney test. Additional NSG mice underwent survival analyses with Kaplan-Meier curves and a log rank (Mantel-Cox) test. Results: At 2 weeks post-treatment, BLI and MRI scans revealed significant reduction in tumor size for CLIO-ICT plus radiation treated tumors compared to monotherapy or vehicle-treated tumors. Combining CLIO-ICT with radiation therapy significantly decreased microvessel density, decreased GICs, increased caspase-3 expression, and prolonged the survival of GBM-bearing mice. CLIO-ICT delivery to GBM could be monitored with MRI. and was not significantly different before and after radiation. There was no significant caspase-3 expression in normal brain at therapeutic doses of CLIO-ICT administered. Conclusion: Our data shows additive anti-tumor effects of CLIO-ICT nanoparticles in combination with radiotherapy. The combination therapy proposed here could potentially be a clinically translatable strategy for treating GBMs.