Mechanism of Action

After IV injection, the ferumoxtran-10 particles are taken up by macrophages, and are transported to the interstitial space and from there through the lymph vessels to the lymph nodes (Figure 3.1). Thus, this contrast agent is cell-specific for macrophages. Once within normally functioning nodes, the intracellular

Figure 3.1. Uptake mechanism of ferumoxtran-10. IV injected particles slowly extravasate from vascular to interstitial space (1) and are then transported to lymph nodes via lymphatic vessels (2). In lymph nodes, particles are internalized by macrophages (3), and these intracellular iron-containing particles cause normal nodal tissue to have low signal intensity. Disturbances of lymph flow or nodal architecture by metastases lead to abnormal accumulation patterns depicted by the lack of decreased signal intensity (4). Reprinted with permission from Deserno et al. (2004).

Figure 3.1. Uptake mechanism of ferumoxtran-10. IV injected particles slowly extravasate from vascular to interstitial space (1) and are then transported to lymph nodes via lymphatic vessels (2). In lymph nodes, particles are internalized by macrophages (3), and these intracellular iron-containing particles cause normal nodal tissue to have low signal intensity. Disturbances of lymph flow or nodal architecture by metastases lead to abnormal accumulation patterns depicted by the lack of decreased signal intensity (4). Reprinted with permission from Deserno et al. (2004).

ferumoxtran-10 within the macrophages reduces the signal intensity of normal node tissue, because of the T2*-susceptibility effects induced by the iron oxide, producing a signal drop or negative contrast enhancement. In areas of lymph nodes that are involved with malignant cells, macrophages are replaced by cancer cells. Therefore, in these areas there is no uptake of the ferumoxtran-10 particles. In addition, due to increased vascular permeability and increased diffusion in cancer tissue, there is minimal leakage of ferumoxtran-10 particles into the extra-cellular space of malignant metastatic areas, which produces a low local concentration and non-clustering of ferumoxtran-10 particles at these sites (Gerlowski and Jain 1986). Through their T1-relaxivity this can induce an increase in signal intensity on T1-weighted images, producing positive enhancement (Bellin et al., 1998). Thus, the ability of post-ferumoxtran-10 MRI to identify metastatic areas in the lymph nodes depends primarily on the degree of uptake of ferumoxtran-10 by the macrophages in normal lymph node tissue and the leakage of ferumoxtran-10 particles in the metastatic area itself. Twenty-four hours after IV injection of ferumoxtran-10, normal lymph node and malignant tissue have different signal intensity on MR images. Therefore, this non-invasive technique may result in the detection of metastatic deposits in normal-sized nodes (Figure 3.2).

Optimal evaluation of post-ferumoxtran-10 images should be done by comparing pre- with post-contrast MR images in the same plane. On the pre-contrast images, the shape, the size, and the location of the nodes can be assessed. On the post-contrast MRI the signal intensity change can be evaluated. However, this requires two MRI examinations, which limits this technique. This problem can be solved by only making a post-ferumoxtran-10 MR exam, using both

Figure 3.2. Normal node and small positive node in a 60-year-old male with prostate cancer. A CT scan in semi-sagittal plane shows normal size (6 mm) node (circle). B Post-ferumoxtran-10 Tj-weighted TSE MR image (which is insensitive to iron) shows two gray normal size nodes (circle, arrow). C On post-ferumoxtran-10 T2*-weighted MEDIC MR image (which is iron sensitive) one node is black (arrow) and the other is white (circle). On histopathology the black node was normal and the white node completely metastatic.

Figure 3.2. Normal node and small positive node in a 60-year-old male with prostate cancer. A CT scan in semi-sagittal plane shows normal size (6 mm) node (circle). B Post-ferumoxtran-10 Tj-weighted TSE MR image (which is insensitive to iron) shows two gray normal size nodes (circle, arrow). C On post-ferumoxtran-10 T2*-weighted MEDIC MR image (which is iron sensitive) one node is black (arrow) and the other is white (circle). On histopathology the black node was normal and the white node completely metastatic.

Figure 3.3. A 58-year-old patient treated for prostate cancer with nodal recurrence. CT and MRI obtained 2 years after lymphadenectomy, prostatectomy and hormonal therapy, with the PSA value increasing from 0 to 1.8. A CT scan in axial plane shows three normal-sized nodes (circle right 5 mm; circle left 2 mm). B Post-ferumoxtran-10 T1 -weighted TSE MR image (which is insensitive to iron) shows the same three gray nodes (circles, arrow). C On post-ferumoxtran-10 T|-weighted MEDIC MR image (which is iron sensitive) one node is black (arrow) and the other two are white (circles). On histopathology, the black node was normal and the white ones were metastatic.

Figure 3.3. A 58-year-old patient treated for prostate cancer with nodal recurrence. CT and MRI obtained 2 years after lymphadenectomy, prostatectomy and hormonal therapy, with the PSA value increasing from 0 to 1.8. A CT scan in axial plane shows three normal-sized nodes (circle right 5 mm; circle left 2 mm). B Post-ferumoxtran-10 T1 -weighted TSE MR image (which is insensitive to iron) shows the same three gray nodes (circles, arrow). C On post-ferumoxtran-10 T|-weighted MEDIC MR image (which is iron sensitive) one node is black (arrow) and the other two are white (circles). On histopathology, the black node was normal and the white ones were metastatic.

a sequence which is insensitive for iron using a T1- or proton-weighted TSE sequences and a sequence which is sensitive for iron. For the latter purpose, a good sequence is a high resolution T2*-weighted MEDIC (TE~18ms). The T1/PW TSE sequences yield high-resolution images without (susceptibility) artefacts (i.e., insensitive to iron), whereas the T2*-sequences provides information about the iron content of the nodes. It is, therefore, important to apply both sequences with the same resolution and slice-positioning parameters. In pelvic tumours (prostate cancer), this can be best done in a plane parallel to the psoas muscles (obturator, or semi-sagittal plane, Figure 3.2), and the axial plane, covering the para-aortic until the femoral region (Figure 3.3). In the 'reading' of the images, a one-by-one comparison gives the best results (Figure 3.2). Incidentally in this way, even a 2 mm metastatic node can be found (Figure 3.3).

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  • karla
    Why contrast med mexhanismof action?
    3 years ago

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