Abstract
Physiological responses such as chronic inflammation and angiogenesis could be used as biomarkers for early detection of cancer with noninvasive imaging modalities. The present study reports the application of magnetic resonance imaging instrument to image the binding of ferrioxamine with hemin that allows visualizing the chronic inflammation foci of lung tissue of immunocompromised rats xenografted using small cell lung carcinoma. A low concentration of ferrioxamine (0.05 ± 0.02 μM·kg−1 of rat weight) deposited on tissue outside the vasculature was found to diffuse across the capillary walls to the interstitial space and inflammation foci, which provided a clear enhancement of T1-weighted gradient-echo sequence images. Ferrioxamine imaging allowed the determination of inflammatory sites and their localization in 3D fat-suppressed maximum intensity projections. The smallest dimension of foci that can be clearly determined is about 0.1 mm3. In concomitant to the in vivo imaging, analysis of histological tissue section showed the development of inflammatory sites. This study provides evidence that medical imaging instrument such as MRI scanner allows researchers to correlate images taken with MRI with those using high-resolution microscopy. Moreover, ferrioxamine is a useful molecular probe for determining chronic inflammation particularly at the very early stages of cancer.
Highlights
Tumor-bearing animals offer a variety of xenograft-based cancer models may greatly help understanding cancer biology, especially for the interactions among cancer cells and normal cells in vivo situation
Kaartinen et al [6] and Hoogenhout et al [4] showed that Wistar rats treated with cyclosporin A develop a state of immune suppression that permits the growth of tumor xenografts
DFO alone is moderately toxic against small cell lung carcinoma (GLC4; IC50 = 30 ± 6 μM) and its corresponding multidrug resistant cells which overexpressed MRP1-protein (IC50 = 50 ± 3 μM) compared with Pirarubicin, (GLC4, IC50 = 10 ± 3 nM and GLC4/adr, IC50 = 42±5 nM)
Summary
Tumor-bearing animals offer a variety of xenograft-based cancer models may greatly help understanding cancer biology, especially for the interactions among cancer cells and normal cells in vivo situation. For this purpose the need of tumor-bearing animal models that can be elucidating the behaviour of cancer cells when faced to the host immunity pressure. This was followed by the appearance of cancer stromal as well as angiogenesis These events can International Journal of Molecular Imaging be clearly visualized by the immunohistochemical staining of endothelial cells and hematoxylin-eosin staining of red blood cells as well as leucocytes accumulation found outside the blood vessels of the tissue. Its mechanism of action appears to be selective for lymphocytes and may interrupt the necessary cellular signals required for proliferation of alloreactive T-cells [7, 8]
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