In vivo preclinical low field MRI monitoring of tumor growth following a suicide gene therapy in an orthotopic mice model of human glioblastoma

Breton, Élodie; Goetz, Christian; Kintz, Jacqueline; Aubertin, G.; Grellier, Bernard; Erbs, Philippe; Rooke, Ronald; Constantinesco, A.; Choquet, Philippe

doi:10.1016/j.crvi.2009.12.012

Cited by 11 publications

(9 citation statements)

References 25 publications

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“…MRI provides detailed information on anatomy and function, and this technique is commonly used for cell tracking assays in vivo in combination with contrast agents, such as superparamagnetic iron oxide nanoparticles (SPIONs). The growing interest related to the use of contrast agents to visualize the migration and growth of cells (e.g., stem cells or tumor cells) has made MRI a particularly interesting technique, as it can enable monitoring studies of cell migration and homing in vivo (8)(9)(10)(11) . Cells labeled with SPIONs for both in vivo and in vitro assays induce a strong contrast in T 2 maps, which facilitates the monitoring of grafted cells.…”

Section: Introductionmentioning

confidence: 99%

In vivo magnetic resonance imaging tracking of C6 glioma cells labeled with superparamagnetic iron oxide nanoparticles

Mamani

Malheiros

Cardoso

et al. 2012

Einstein (São Paulo)

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Objective: The aim of the current study was to monitor the migration of superparamagnetic iron oxide nanoparticle (SPION)-labeled C6 cells, which were used to induce glioblastoma tumor growth in an animal model, over time using magnetic resonance imaging (MRI), with the goal of aiding in tumor prognosis and therapy. Methods: Two groups of male Wistar rats were used for the tumor induction model. In the first group (n=3), the tumors were induced via the injection of SPION-labeled C6 cells. In the second group (n=3), the tumors were induced via the injection of unlabeled C6 cells. Prussian Blue staining was performed to analyze the SPION distribution within the C6 cells in vitro. Tumor-inducing C6 cells were injected into the right frontal cortex, and subsequent tumor monitoring and SPION detection were performed using T 2 -and T 2 *-weighted MRI at a 2T field strength. In addition, cancerous tissue was histologically analyzed after performing the MRI studies. Results: The in vitro qualitative evaluation demonstrated adequate distribution and satisfactory cell labeling of the SPIONs. At 14 or 21 days after C6 injection, a SPIONinduced T 2 -and T 2 *-weighted MRI signal reduction was observed within the lesion located in the left frontal lobe on parasagittal topography. Moreover, histological staining of the tumor tissue with Prussian Blue revealed a broad distribution of SPIONs within the C6 cells. Conclusion: MRI analyses exhibit potential for monitoring the tumor growth of C6 cells efficiently labeled with SPIONs.

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Section: Introductionmentioning

confidence: 99%

In vivo magnetic resonance imaging tracking of C6 glioma cells labeled with superparamagnetic iron oxide nanoparticles

Mamani

Malheiros

Cardoso

et al. 2012

Einstein (São Paulo)

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“…The expression of CD, in presence of 5-FC, not only induced cell death and a bystander effect (27,28), but also led to radiosensitization in various cancer models (29,30). Breton and colleagues performed a study using a modified Ankara virus to express yeast CD in situ, reducing tumor growth in a glioblastoma mouse model (10). After introducing a viral vector for in vitro transformation of several cancer cell lines (12,31) and evaluation in preclinical models (32) not detected significant immunogenicity of bCD in animals (33,34).…”

Section: Discussionmentioning

confidence: 99%

“…To minimize sideeffects of 5-FU, targeted delivery of bCD to tumor cells coupled with systemic administration of 5-FC is also being considered. Monoclonal antibodies conjugated to the enzyme, as well as viral vectors and non-viral vectors, have been used to achieve this goal (6)(7)(8)(9)(10)(11)(12)(13). Recent studies have demonstrated prostate cancer cell-specific nanoparticle delivery of bCD to tumor xenografts by specific targeting of prostate-specific membrane antigen that resulted in improved tumor control (13,14) following localized conversion of 5-FC to 5-FU.…”

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confidence: 99%

Delayed Progression of Lung Metastases Following Delivery of a Prodrug-activating Enzyme

Doré-Savard

Chen

Winnard

et al. 2017

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Despite significant improvements in the treatment of primary cancer, successful treatment of metastatic disease remains a challenge. Indeed, the 5-year survival rate for patients with tumors distant from the primary site has not significantly improved in the past decade (1). The search for an alternative to systemic chemotherapy has thus been a priority, especially in the context of metastases.Prodrug/enzyme treatments have been used to circumvent some side-effects of chemotherapy (2, 3). One of the enzymes that has met with some success is bacterial cytosine deaminase (bCD) from Escherichia coli. bCD converts the non-toxic prodrug 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU) (4). The latter potent chemotherapeutic agent has been used for decades in therapy of colorectal, head and neck, and breast cancer, among others. It is, however, associated with debilitating side-effects such as cardiotoxicity, diarrhea and myelosuppression (5) since high doses of systemic 5-FU are required to achieve significant tumor concentrations. To minimize sideeffects of 5-FU, targeted delivery of bCD to tumor cells coupled with systemic administration of 5-FC is also being considered. Monoclonal antibodies conjugated to the enzyme, as well as viral vectors and non-viral vectors, have been used to achieve this goal (6-13). Recent studies have demonstrated prostate cancer cell-specific nanoparticle delivery of bCD to tumor xenografts by specific targeting of prostate-specific membrane antigen that resulted in improved tumor control (13,14) following localized conversion of 5-FC to 5-FU.However, many types of cancer do not express cancer cell-specific surface receptors or antigens, making it important to determine the effect of 5-FU formed from bCD in the absence of targeted delivery. The therapeutic effect of bCD/5-FC in a metastatic disease setting remains sparsely evaluated (15-17). Our purpose in this study was to evaluate bCD/5-FC treatment in the metastatic setting.Several mutants have been created for an enhanced conversion rate of 5-FC to . A triple-mutant (bCD 1525 ) displaying high specificity for 5-FC (21) exhibited increased antitumor activity and also bystander effect, a phenomenon by which the cytotoxic metabolite is transferred to nearby cells via gap junction intercellular communications (22, 23). Here we used the bCD 1525 triple-mutant enzyme to 2195

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“…1,3,19,32,39,44,45,[50][51][52][53][54][55][56] It is not unusual that drugs that appear very promising in preclinical trials have disappointing clinical results.…”

Section: Applications In Preclinical Trialsmentioning

confidence: 99%

“…19,39,[44][45][46][51][52][53][54][55][56] Moffat et al 52 compared tumor growth, perfusion parameters, and chemotherapy effectiveness in wild type, VEGF-A overexpressing, and VEGF-A underexpressing 9L gliosarcoma rat xenografts. Perfusion parameters, CBV and CBF, were quantified both by DSC-PWI and continuous arterial spin-labeling and were confronted with MVD and immunohistochemical and genetic analysis by real-time quantitative polymerase chain reaction.…”

Section: Applications In Preclinical Trialsmentioning

confidence: 99%

MR Imaging Features of High-Grade Gliomas in Murine Models: How They Compare with Human Disease, Reflect Tumor Biology, and Play a Role in Preclinical Trials

Borges¹,

López‐Larrubia²,

Marques³

et al. 2011

AJNR Am J Neuroradiol

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SUMMARY: Murine models are the most commonly used and best investigated among the animal models of HGG. They constitute an important weapon in the development and testing of new anticancer drugs and have long been used in preclinical trials. Neuroimaging methods, particularly MR imaging, offer important advantages for the evaluation of treatment response: shorter and more reliable treatment end points and insight on tumor biology and physiology through the use of functional imaging DWI, PWI, BOLD, and MR spectroscopy. This functional information has been progressively consolidated as a surrogate marker of tumor biology and genetics and may play a pivotal role in the assessment of specifically targeted drugs, both in clinical and preclinical trials. The purpose of this Research Perspectives was to compile, summarize, and critically assess the available information on the neuroimaging features of different murine models of HGGs, and explain how these correlate with human disease and reflect tumor biology.ABBREVIATIONS: AIF ϭ arterial input function; ATP ϭ adenosine triphosphate; BOLD ϭ blood oxygen level-dependent; DCE ϭ dynamic contrast-enhanced; DSC ϭ dynamic susceptibility contrast; FLASH ϭ fast low-angle shot; gadolinium-DTPA ϭ gadolinium-diethylene-triamine pentaacetic acid; GEMM ϭ genetically engineered mouse model; GRE ϭ gradient recalled-echo; HGG ϭ high-grade glioma; MMP2 ϭ matrix metalloproteinase type 2; MVD ϭ mean vascular density; rCBVϭ relative cerebral blood volume; VEGF ϭ vascular endothelial growth factor A nimal models of HGG have become an imperative tool in the development and testing of new anticancer drugs. The combination of these advanced neuroimaging methods provides a novel integrated environment in which a collection of noninvasive biomarkers validated on well-defined animal models may provide important clues to tumor biology and response to treatment, with potential applications in human neoplasms. In general, the use of animal models overcomes many of the limitations found in the clinical setting, including impracticable serial tissue sampling and difficulties in establishing correlations between tumor physiopathology and its genetic profile, a circumstance limiting considerably the successful implementation of tailored personalized cancer treatments.Among neuroimaging methods, MR imaging is the most common technique to assist the management of patients with brain tumors; it is free of ionizing radiation, overall well-tolerated, and provides detailed anatomic and functional information. Neuroimaging features of murine models of HGG have been less explored due to technical limitations. Highresolution MR imaging of small animals requires high-field magnets with small bores and dedicated coils, adequate anesthesia, and tailored fixation devices (Fig 1).Murines are the most commonly used and are the best investigated models of human glioma. They are easy to handle, have a short life span, and develop central nervous system tumors that are similar to their human counterparts.1,2 Moreover, t...

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In vivo preclinical low field MRI monitoring of tumor growth following a suicide gene therapy in an orthotopic mice model of human glioblastoma

Cited by 11 publications

References 25 publications

In vivo magnetic resonance imaging tracking of C6 glioma cells labeled with superparamagnetic iron oxide nanoparticles

In vivo magnetic resonance imaging tracking of C6 glioma cells labeled with superparamagnetic iron oxide nanoparticles

Delayed Progression of Lung Metastases Following Delivery of a Prodrug-activating Enzyme

MR Imaging Features of High-Grade Gliomas in Murine Models: How They Compare with Human Disease, Reflect Tumor Biology, and Play a Role in Preclinical Trials

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