Multiparametric MR imaging of tumor response to intraarterial chemotherapy in orthotopic xenograft models of human metastatic brain tumor

Kim, Byung Jun; Kim, Keonha; Im, Keun Ho; Kim, Jae-Hoon; Lee, Jun Young; Jeon, Pyoung; Byun, Hongsik

doi:10.1007/s11060-015-2041-5

Cited by 7 publications

(5 citation statements)

References 30 publications

(35 reference statements)

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“…chemotherapy (internal carotid artery) compared with i.v. chemotherapy (tail vein), similar to our study [ 38 ]. This demonstrates that even difficult-to-access tumor entities can be treated with i.a.…”

Section: Discussionsupporting

confidence: 91%

Evaluation of intraarterial and intravenous cisplatin chemotherapy in the treatment of metastatic osteosarcoma using an orthotopic xenograft mouse model

Robl

Botter

Pellegrini

et al. 2016

J Exp Clin Cancer Res

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BackgroundOsteosarcoma is the most common primary malignancy of bone. Its treatment relies on the administration of neoadjuvant and adjuvant chemotherapy combined with surgery. Alternative to common intravenous (i.v.) administration of chemotherapeutic drugs, clinical studies also evaluated the benefit of intraarterial (i.a.) administrations. However, conflicting results were obtained when both routes of administration of cisplatin (CDDP), a gold standard drug in osteosarcoma treatment, were compared. In order to overcome clinical confounding factors, we evaluated both routes of drug administration in a mouse model of experimental osteosarcoma.MethodsWe directly compared i.v. versus i.a. drug infusions of cisplatin (CDDP), in an orthotopic xenograft mouse model of metastatic osteosarcoma. We performed tumor monitoring using caliper and micro computed tomography and measured tumor perfusion using laser speckle contrast imaging. Histopathological changes were evaluated using hematoxylin and eosin staining as well as immunohistochemistry (cleaved PARP-1, CD31, HIF-1α).ResultsFirst, an effective concentration of 4 mg/kg i.a. CDDP was determined that significantly reduced primary tumor volume. We used this concentration of i.a. CDDP and compared it to infusions of i.v. CDDP. Systemic (i.v.) CDDP only showed minor suppression of tumor growth whereas local (i.a.) CDDP strongly inhibited tumor growth and destruction of cortical bone in the tumor-bearing hind limb. Inhibition of tumor growth was linked to a reduced blood perfusion and resulted in increased amounts of tumor necrosis after i.a. CDDP. After treatment with i.a. CDDP, remaining viable tumor tissue responded by increasing expression of HIF-1α. Side effects due to administration of CDDP were minor, showing no differences in kidney damage between i.v. and i.a. CDDP. However, increased epidermal apoptosis in the foot was an indirect marker for locally increased concentrations of CDDP.ConclusionsOur findings demonstrate the great potential of local administration of cytotoxic chemotherapeutics, such as CDDP. Consequently, we provide a preclinical basis for a renewed interest in the clinical use of i.a. chemotherapy in osteosarcoma therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0392-1) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 91%

Evaluation of intraarterial and intravenous cisplatin chemotherapy in the treatment of metastatic osteosarcoma using an orthotopic xenograft mouse model

Robl

Botter

Pellegrini

et al. 2016

J Exp Clin Cancer Res

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“…Intracranial tumours derived from MDA‐MB‐231 LM2–4 cells, isolated from a lung metastasis following orthotopic implantation of MDA‐MB‐231 cells, which grow in a partially expansive, partially invasive manner, were therefore included in this study as a model of invasive tumour growth in the brain. Intracranial injection of parental MDA‐MB‐231 cells has also been used to provide a model of metastatic brain disease …”

Section: Discussionmentioning

confidence: 63%

“…Intracranial injection of parental MDA-MB-231 cells has also been used to provide a model of metastatic brain disease. 29 Interesting differences were apparent in the vascular phenotypes of the two tumour models studied. MDA-MB-231 LM2-4 tumours demonstrated higher ΔR 1 than RG2 tumours, indicative of a higher degree of extravasation of contrast agent, hence more permeable vasculature.…”

Section: Discussionmentioning

confidence: 98%

Investigating intracranial tumour growth patterns with multiparametric MRI incorporating Gd‐DTPA and USPIO‐enhanced imaging

et al. 2016

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High grade and metastatic brain tumours exhibit considerable spatial variations in proliferation, angiogenesis, invasion, necrosis and oedema. Vascular heterogeneity arising from vascular co‐option in regions of invasive growth (in which the blood–brain barrier remains intact) and neoangiogenesis is a major challenge faced in the assessment of brain tumours by conventional MRI.A multiparametric MRI approach, incorporating native measurements and both Gd‐DTPA (Magnevist) and ultrasmall superparamagnetic iron oxide (P904)‐enhanced imaging, was used in combination with histogram and unsupervised cluster analysis using a k‐means algorithm to examine the spatial distribution of vascular parameters, water diffusion characteristics and invasion in intracranially propagated rat RG2 gliomas and human MDA‐MB‐231 LM2–4 breast adenocarcinomas in mice.Both tumour models presented with higher ΔR 1 (the change in transverse relaxation rate R 1 induced by Gd‐DTPA), fractional blood volume (fBV) and apparent diffusion coefficient than uninvolved regions of the brain. MDA‐MB‐231 LM2–4 tumours were less densely cellular than RG2 tumours and exhibited substantial local invasion, associated with oedema, whereas invasion in RG2 tumours was minimal. These additional features were reflected in the more heterogeneous appearance of MDA‐MB‐231 LM2–4 tumours on T 2‐weighted images and maps of functional MRI parameters.Unsupervised cluster analysis separated subregions with distinct functional properties; areas with a low fBV and relatively impermeable blood vessels (low ΔR 1) were predominantly located at the tumour margins, regions of MDA‐MB‐231 LM2–4 tumours with relatively high levels of water diffusion and low vascular permeability and/or fBV corresponded to histologically identified regions of invasion and oedema, and areas of mismatch between vascular permeability and blood volume were identified.We demonstrate that dual contrast MRI and evaluation of tissue diffusion properties, coupled with cluster analysis, allows for the assessment of heterogeneity within invasive brain tumours and the designation of functionally diverse subregions that may provide more informative predictive biomarkers.

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“…injection (Yang et al 2016). Other modes of applications are possible as well, such as subcutaneous (Kenmogne et al 2015), intratumoral (Jiang et al 2016 or intraarterial (carotid artery) (Kim et al 2016).…”

Section: Models Of Tumor Induction In Athymic Nude Micementioning

confidence: 99%

Athymic Nude Mice as an Experimental Model for Cancer Treatment

Szadvári

Križanová²,

Babula

2016

Physiol Res

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Athymic nude mice, a murine strain bearing spontaneous deletion in the Foxn1 gene that causes deteriorated or absent thymus (which results in inhibited immune system with reduction of number of T cells), represent a widely used model in cancer research having long lasting history as a tool for preclinical testing of drugs. The review describes three models of athymic mice that utilize cancer cell lines to induce tumors. In addition, various methods that can be applied in order to evaluate activity of anticancer agents in these models are shown and discussed. Although each model has certain disadvantages, they are still considered as inevitable instruments in many fields of cancer research, particularly in finding new drugs that would more effectively combat the cancer disease or enhance the use of current chemotherapy. Finally, the review summarizes strengths and weaknesses as well as future perspectives of the athymic nude mice model in cancer research.

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Multiparametric MR imaging of tumor response to intraarterial chemotherapy in orthotopic xenograft models of human metastatic brain tumor

Cited by 7 publications

References 30 publications

Evaluation of intraarterial and intravenous cisplatin chemotherapy in the treatment of metastatic osteosarcoma using an orthotopic xenograft mouse model

Evaluation of intraarterial and intravenous cisplatin chemotherapy in the treatment of metastatic osteosarcoma using an orthotopic xenograft mouse model

Investigating intracranial tumour growth patterns with multiparametric MRI incorporating Gd‐DTPA and USPIO‐enhanced imaging

Athymic Nude Mice as an Experimental Model for Cancer Treatment

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