Summary

Мульти-модальных изображений ангиогенеза в обнаженной модели крысы из груди метастазы рака костей с помощью магнитного резонанса, компьютерной томографии Объемные и ультразвуковые

Published: August 14, 2012
doi:

Summary

В патогенезе костных метастазов, ангиогенез является важным процессом и, следовательно, представляет собой мишень для визуализации и терапии. Здесь мы представляем крысиной модели конкретных участков груди метастазы рака костей и описать стратегии неинвазивно изображения кровеносных сосудов<em> В естественных условиях</em> С помощью магнитно-резонансная томография, компьютерная томография объемный и УЗИ.

Abstract

Angiogenesis is an essential feature of cancer growth and metastasis formation. In bone metastasis, angiogenic factors are pivotal for tumor cell proliferation in the bone marrow cavity as well as for interaction of tumor and bone cells resulting in local bone destruction. Our aim was to develop a model of experimental bone metastasis that allows in vivo assessment of angiogenesis in skeletal lesions using non-invasive imaging techniques.

For this purpose, we injected 105 MDA-MB-231 human breast cancer cells into the superficial epigastric artery, which precludes the growth of metastases in body areas other than the respective hind leg1. Following 25-30 days after tumor cell inoculation, site-specific bone metastases develop, restricted to the distal femur, proximal tibia and proximal fibula1. Morphological and functional aspects of angiogenesis can be investigated longitudinally in bone metastases using magnetic resonance imaging (MRI), volumetric computed tomography (VCT) and ultrasound (US).

MRI displays morphologic information on the soft tissue part of bone metastases that is initially confined to the bone marrow cavity and subsequently exceeds cortical bone while progressing. Using dynamic contrast-enhanced MRI (DCE-MRI) functional data including regional blood volume, perfusion and vessel permeability can be obtained and quantified2-4. Bone destruction is captured in high resolution using morphological VCT imaging. Complementary to MRI findings, osteolytic lesions can be located adjacent to sites of intramedullary tumor growth. After contrast agent application, VCT angiography reveals the macrovessel architecture in bone metastases in high resolution, and DCE-VCT enables insight in the microcirculation of these lesions5,6. US is applicable to assess morphological and functional features from skeletal lesions due to local osteolysis of cortical bone. Using B-mode and Doppler techniques, structure and perfusion of the soft tissue metastases can be evaluated, respectively. DCE-US allows for real-time imaging of vascularization in bone metastases after injection of microbubbles7.

In conclusion, in a model of site-specific breast cancer bone metastases multi-modal imaging techniques including MRI, VCT and US offer complementary information on morphology and functional parameters of angiogenesis in these skeletal lesions.

Protocol

1. Культуре клеток Культура MDA-MB-231 человеческих клеток рака молочной железы (Американская коллекция типовых культур) в RPMI-1640 (Invitrogen, Германия) с добавлением 10% FCS (Sigma, Германия). Держите всех культур в стандартных условиях (37 ° C, увлажненной атмосфере 5% CO 2) и прохождение клеток 2-…

Discussion

Метод вызывая экспериментальные метастазы в кости, представленные здесь, в сочетании с изображениями процедуры позволяют последующих остеолитические поражения в обнаженном крыс в продольном направлении. В нашей модели MDA-MB-231 человеческих клеток рака молочной железы вводят в море, ко…

Disclosures

The authors have nothing to disclose.

Acknowledgements

Эта работа была поддержана Deutsche Forschungsgemeinschaft (SFB-TR 23 и SFB-TR 79, туберкулезом и DK). Авторы хотели бы поблагодарить Ренате Bangert Карин Leotta и Лиза Зейлера за отличную техническую помощь.

Materials

Name of the reagent Company Catalogue number
MDA-MB-231 human breast cancer cells American Type Culture Collection (ATCC) HTB-26
RPMI-1640 Invitrogen 61870
FCS Invitrogen 10270
Trypsin-EDTA Invitrogen 25300
Carprofen Rimadyl Pfizer PZN 110208
Magnevist Bayer-Schering PZN 6961516
Imeron 400 MCT Bracco PZN 228654
SonoVue Bracco PZN 1567358
Papaverin Alfa Aesar L 04152
Isofluran Baxter HDG 9623
Symphony (Magnetic resonance imaging) Siemens  
Volume CT (Volumetric computed tomography) Siemens  
Acuson Sequioa 512 (Ultrasound) Siemens-Acuson  

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Cite This Article
Bäuerle, T., Komljenovic, D., Berger, M. R., Semmler, W. Multi-modal Imaging of Angiogenesis in a Nude Rat Model of Breast Cancer Bone Metastasis Using Magnetic Resonance Imaging, Volumetric Computed Tomography and Ultrasound. J. Vis. Exp. (66), e4178, doi:10.3791/4178 (2012).

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