MRI of Blood Volume and Cellular Uptake of Superparamagnetic Iron in an Animal Model of Choroidal Melanoma

Krause, Matthias; Kwong, Kenneth K.; Xiong, Ji; Gragoudas, Evangelos S.; Young, Lucy H.

doi:10.1159/000063883

Cited by 19 publications

(9 citation statements)

References 58 publications

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“…14 Intravenously administered iron oxide nanoparticles have been shown to accumulate in tumor tissue and allow noninvasive tumor detection and monitoring by MRI in brain gliomas, 21 squamous cell flank carcinomas, 22 and choroidal melanomas. 23 Indeed, SPIONs are already used in MRI-based tumor detection in liver cancer, 24 and are currently in clinical trials to differentiate metastatic from inflammatory lymph nodes. 18 …”

Section: Introductionmentioning

confidence: 99%

Theranostic Application of Mixed Gold and Superparamagnetic Iron Oxide Nanoparticle Micelles in Glioblastoma Multiforme

Sun¹,

Joh²,

Al-Zaki³

et al. 2016

j biomed nanotechnol

104

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The treatment of glioblastoma multiforme, the most prevalent and lethal form of brain cancer in humans, has been limited in part by poor delivery of drugs through the blood-brain barrier and by unclear delineation of the extent of infiltrating tumor margins. Nanoparticles, which selectively accumulate in tumor tissue due to their leaky vasculature and the enhanced permeability and retention effect, have shown promise as both therapeutic and diagnostic agents for brain tumors. In particular, superparamagnetic iron oxide nanoparticles (SPIONs) have been leveraged as T2-weighted MRI contrast agents for tumor detection and imaging; and gold nanoparticles (AuNP) have been demonstrated as radiosensitizers capable of propagating electron and free radical-induced radiation damage to tumor cells. In this study, we investigated the potential applications of novel gold and SPION-loaded micelles (GSMs) coated by polyethylene glycol-polycaprolactone (PEG-PCL) polymer. By quantifying gh2ax DNA damage foci in glioblastoma cell lines, we tested the radiosensitizing efficacy of these GSMs, and found that GSM administration in conjunction with radiation therapy (RT) led to ~2-fold increase in density of double-stranded DNA breaks. For imaging, we used GSMs as a contrast agent for both computed tomography (CT) and magnetic resonance imaging (MRI) studies of stereotactically implanted GBM tumors in a mouse model, and found that MRI but not CT was sufficiently sensitive to detect and delineate tumor borders after administration and accumulation of GSMs. These results suggest that with further development and testing, GSMs may potentially be integrated into both imaging and treatment of brain tumors, serving a theranostic purpose as both an MRI-based contrast agent and a radiosensitizer.

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Section: Introductionmentioning

confidence: 99%

Theranostic Application of Mixed Gold and Superparamagnetic Iron Oxide Nanoparticle Micelles in Glioblastoma Multiforme

Sun¹,

Joh²,

Al-Zaki³

et al. 2016

j biomed nanotechnol

104

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show abstract

“…Ultrasound is able to give a rough estimation of the melanoma size but, because of its limited penetration depth, little information can be obtained on the internal structure of the melanoma. MRI has recently been used to study uveal melanoma in different animal models . MRI is not only able to show the internal structure of the melanoma, but may also be able to demonstrate whether the melanoma has grown through the sclera, which can lead to rapid metastasis throughout the body.…”

Section: Resultsmentioning

confidence: 99%

High‐resolution MRI of uveal melanoma using a microcoil phased array at 7 T

et al. 2013

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High-field MRI is a promising technique for the characterisation of ocular tumours, both in vivo and after enucleation. For in vivo imaging at 7 T, a dedicated three-element microcoil array was constructed as a high-sensitivity receive-only device. Using a dedicated blink/fixation protocol, high-resolution in vivo images could be acquired within 3 min in volunteers and patients with no requirement for post-acquisition image registration. Quantitative measures of axial length, aqueous depth and lens thickness in a healthy volunteer were found to agree well with standard ocular biometric techniques. In a patient with uveal melanoma, in vivo MRI gave excellent tumour/aqueous body contrast. Ex vivo imaging of the enucleated eye showed significant heterogeneity within the tumour.

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“…However, rapid tumor growth and other complications have repelled this model. Approaches of grafting murine B16F10 cells into rabbit eyes resulted indeed in solid ocular tumors but metastases were not reliably observed and immune suppression was necessary which represented a disadvantage of this model [ 44 , 45 ].…”

Section: Animal Models Of Uveal Melanomamentioning

confidence: 99%

Animal Models of Uveal Melanoma: Methods, Applicability, and Limitations

Stei

Loeffler

Holz

et al. 2016

BioMed Research International

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Animal models serve as powerful tools for investigating the pathobiology of cancer, identifying relevant pathways, and developing novel therapeutic agents. They have facilitated rapid scientific progress in many tumor entities. However, for establishing a powerful animal model of uveal melanoma fundamental challenges remain. To date, no animal model offers specific genetic attributes as well as histologic, immunologic, and metastatic features of uveal melanoma. Syngeneic models with intraocular injection of cutaneous melanoma cells may suit best for investigating immunologic/tumor biology aspects. However, differences between cutaneous and uveal melanoma regarding genetics and metastasis remain problematic. Human xenograft models are widely used for evaluating novel therapeutics but require immunosuppression to allow tumor growth. New approaches aim to establish transgenic mouse models of spontaneous uveal melanoma which recently provided preliminary promising results. Each model provides certain benefits and may render them suitable for answering a respective scientific question. However, all existing models also exhibit relevant limitations which may have led to delayed research progress. Despite refined therapeutic options for the primary ocular tumor, patients' prognosis has not improved since the 1970s. Basic research needs to further focus on a refinement of a potent animal model which mimics uveal melanoma specific mechanisms of progression and metastasis. This review will summarise and interpret existing animal models of uveal melanoma including recent advances in the field.

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MRI of Blood Volume and Cellular Uptake of Superparamagnetic Iron in an Animal Model of Choroidal Melanoma

Cited by 19 publications

References 58 publications

Theranostic Application of Mixed Gold and Superparamagnetic Iron Oxide Nanoparticle Micelles in Glioblastoma Multiforme

Theranostic Application of Mixed Gold and Superparamagnetic Iron Oxide Nanoparticle Micelles in Glioblastoma Multiforme

High‐resolution MRI of uveal melanoma using a microcoil phased array at 7 T

Animal Models of Uveal Melanoma: Methods, Applicability, and Limitations

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