Standardization and Detailed Characterization of the Syngeneic Fischer/F98 Glioma Model

Mathieu, David; Lecomte, Roger; Tsanaclis, Ana Maria Crous; Larouche, Annie; Fortin, David

doi:10.1017/s0317167100006715

Cited by 59 publications

(71 citation statements)

References 51 publications

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“…The rat F98 cell line was chosen because it represents a good model of human glioblastoma [18,19]. The F98 cell line was obtained from ATCC and tested negative for the MAP assay by Charles River Laboratories (Wilmington, MA, USA).…”

Section: Cell Line and Culture Conditionsmentioning

confidence: 99%

Concomitant treatment of F98 glioma cells with new liposomal platinum compounds and ionizing radiation

et al. 2009

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Despite significant advances, the radiotherapy and chemotherapy protocols marginally improve the overall survival of patients with glioblastoma. Lipoplatin ™ , and Lipoxal ™ , the liposomal formulations of cisplatin and oxaliplatin respectively, were tested on the F98 glioma cells for their ability to improve the cell uptake and increase the synergic effect when combined with ionizing radiation. The cytotoxicity and synergic effect of platinum compounds were assessed by colony formation assay, while the cellular uptake was measured by Inductively Coupled Plasma Mass Spectrometer (ICP-MS). After 4 h exposure with platinum compounds, cells were irradiated (1.5 to 6.6 Gy) with a 60 Co source. The liposomal formulations were compared to their liposome-free analogs and to carboplatin. The concomitant treatment of F98 cells with carboplatin and radiation produced the highest radiosensitizing effect (30-fold increase). Among the platinum compounds tested, Lipoplatin ™ produced the most promising results. This liposomal formulation of cisplatin improved the cell uptake by 3-fold, and its radiosensitizing potential was enhanced by 14-fold. Although Lipoxal ™ can potentially reduce the adverse effect of oxaliplatin, a synergic effect with radiation was measured only when incubated at a concentration higher than its IC50. Conversely, concomitant treatment with cisplatin did not result in a synergic effect, as in fact a radioprotective effect was measured on the F98 cells. In conclusion, among the five platinum compounds tested, carboplatin and Lipoplatin ™ showed the best radiosensitizing effect. Lipoplatin ™ seems the most promising since it led to the best cellular incorporation and has already been reported to be less neurotoxic than other platinum compounds.

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Section: Cell Line and Culture Conditionsmentioning

confidence: 99%

Concomitant treatment of F98 glioma cells with new liposomal platinum compounds and ionizing radiation

et al. 2009

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“…The implantation method was described previously. 27 F98 cells (10,000 cells in 5 µL) were prepared and implanted into the right caudate nucleus (1 mm anterior, 3 mm right of the bregma, and 6 mm deep) of the brain in 5 min. The convection-enhanced delivery (CED) procedure 28 was performed 10 days after implantation of F98 cells, at the same injection site using a 33 gauge Hamilton syringe.…”

Section: Convection-enhanced Delivery In F98 Glioma Modelmentioning

confidence: 99%

Development and optimization of an injectable formulation of copper diethyldithiocarbamate, an active anticancer agent

Wehbe¹,

Anantha²,

Shi³

et al. 2017

IJN

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Copper diethyldithiocarbamate (Cu(DDC) 2 ) is the active anticancer agent generated when disulfiram (DSF) is provided in the presence of copper. To date, research directed toward repurposing DSF as an anticancer drug has focused on administration of DSF and copper in combination, efforts that have proven unsuccessful in clinical trials. This is likely due to the inability to form Cu(DDC) 2 at relevant concentrations in regions of tumor growth. Little effort has been directed toward the development of Cu(DDC) 2 because of the inherent aqueous insolubility of the complex. Here, we describe an injectable Cu(DDC) 2 formulation prepared through a method that involves synthesis of Cu(DDC) 2 inside the aqueous core of liposomes. Convection-enhanced delivery of a Cu(DDC) 2 formulation prepared using 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/cholesterol liposomes into a rat model of F98 glioma engendered a 25% increase in median survival time relative to vehicle-treated animals. In a murine subcutaneous MV-4–11 model, treatment resulted in a 45% reduction in tumor burden when compared to controls. Pharmacokinetic studies indicated that the Cu(DDC) 2 was rapidly eliminated after intravenous administration while the liposomes remained in circulation. To test whether liposomal lipid composition could increase Cu(DDC) 2 circulation lifetime, a number of different formulations were evaluated. Studies demonstrated that liposomes composed of DSPC and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-n-(carboxy[polyethylene glycol]-2000) (95:5) enhanced Cu(DDC) 2 concentrations in the circulation as reflected by a 4.2-fold increase in plasma AUC (0−∞) relative to the DSPC/cholesterol formulation. The anticancer activity of this Cu(DDC) 2 formulation was subsequently evaluated in the MV-4–11 model. At its maximum tolerated dose, this formulation exhibited comparable activity to the DSPC/cholesterol formulation. This is the first report demonstrating the therapeutic effects of an injectable Cu(DDC) 2 formulation in vivo.

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“…F98 glioblastoma cells were implanted in the right hemisphere of 17 male Fischer rats (254.6 6 15.9 g, Charles River Laboratories) according to a previously published protocol (13). The animals underwent dynamic PET scans 9-15 d after implantation.…”

Section: Animal Modelmentioning

confidence: 99%

Determination of an Optimal Pharmacokinetic Model of ¹⁸F-FET for Quantitative Applications in Rat Brain Tumors

et al. 2017

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O-(2-18 F-fluoroethyl)-L-tyrosine ( 18 F-FET) is a radiolabeled artificial amino acid used in PET for tumor delineation and grading. The present study compares different kinetic models to determine which are more appropriate for 18 F-FET in rats. Methods: Rats were implanted with F98 glioblastoma cells in the right hemisphere and scanned 9-15 d later. PET data were acquired during 50 min after a 1-min bolus of 18 F-FET. Arterial blood samples were drawn for arterial input function determination. Two compartmental pharmacokinetic models were tested: the 2-tissue model and the 1-tissue model. Their performance at fitting concentration curves from regions of interest was evaluated using the Akaike information criterion, F test, and residual plots. Graphical models were assessed qualitatively. Results: Metrics indicated that the 2-tissue model was superior to the 1-tissue model for the current dataset. The 2-tissue model allowed adequate decoupling of 18 F-FET perfusion and internalization by cells in the different regions of interest. Of the 2 graphical models tested, the Patlak plot provided adequate results for the tumor and brain, whereas the Logan plot was appropriate for muscles. Conclusion: The 2-tissue-compartment model is appropriate to quantify the perfusion and internalization of 18 F-FET by cells in various tissues of the rat, whereas graphical models provide a global measure of uptake. Ther adiolabeled artificial amino acid O-(2-18 F-fluoroethyl)-Ltyrosine ( 18 F-FET) has proven useful for the PET assessment of brain tumors in preclinical and clinical settings (1-3). Its high uptake in tumor tissue compared with normal brain and inflamed tissues allows for efficient tumor delineation (4), but the typical SUVs and tumor-to-brain ratios are of limited use for tumor grading (5,6). In contrast, the shape of time-activity curves are indicative of tumor grade and aggressiveness (7). For example, in untreated or recurring gliomas, continuously ascending curves are associated with a better prognosis than curves that reach a maximum a few minutes after injection (6,8), but the underlying mechanisms remain to be clarified (7,9,10). A pharmacokinetic model could help explain these differences and would allow quantitative comparison of cohorts.There have been few reports on 18 F-FET pharmacokinetic modeling (11,12), and a consensus on the most appropriate models has not been proposed. The present study aims at identifying the best models in different tissue types. MATERIALS AND METHODS Animal ModelExperiments were conducted in accordance with the recommendations of the Canadian Council on Animal Care and the local Ethics Committee. F98 glioblastoma cells were implanted in the right hemisphere of 17 male Fischer rats (254.6 6 15.9 g, Charles River Laboratories) according to a previously published protocol (13). The animals underwent dynamic PET scans 9-15 d after implantation. All imaging procedures were performed under isoflurane anesthesia with breathing rate and temperature continuously monitored. An automatic in...

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Standardization and Detailed Characterization of the Syngeneic Fischer/F98 Glioma Model

Cited by 59 publications

References 51 publications

Concomitant treatment of F98 glioma cells with new liposomal platinum compounds and ionizing radiation

Concomitant treatment of F98 glioma cells with new liposomal platinum compounds and ionizing radiation

Development and optimization of an injectable formulation of copper diethyldithiocarbamate, an active anticancer agent

Determination of an Optimal Pharmacokinetic Model of ¹⁸F-FET for Quantitative Applications in Rat Brain Tumors

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Standardization and Detailed Characterization of the Syngeneic Fischer/F98 Glioma Model

Cited by 59 publications

References 51 publications

Concomitant treatment of F98 glioma cells with new liposomal platinum compounds and ionizing radiation

Concomitant treatment of F98 glioma cells with new liposomal platinum compounds and ionizing radiation

Development and optimization of an injectable formulation of copper diethyldithiocarbamate, an active anticancer agent

Determination of an Optimal Pharmacokinetic Model of 18F-FET for Quantitative Applications in Rat Brain Tumors

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Determination of an Optimal Pharmacokinetic Model of ¹⁸F-FET for Quantitative Applications in Rat Brain Tumors