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.
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.
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…
The authors have nothing to disclose.
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.
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 |