Rudiger Lawaczeck

Magnetic iron oxide particles coated with carboxydextran for parenteral administration and liver contrasting. Pre-clinical profile of SH U555A.

Rationale and objectives: To evaluate the physical and pharmacological profiles of SH U555A, a suspension of magnetic iron oxide particles that is designed to enhance the visualization of liver tumors and metastases. Material and Methods: Chemical and physical methods were used to characterize the size and structure of these magnetic iron oxide particles in aqueous solution. The biodistribution and pharmacokinetics of the particles were studied in mice, rats and dogs. The imaging efficacy of the particles was demonstrated by MR imaging in rat liver tumors Results: The SH U555A particles consist of low-molecular-weight carboxydextran-coated iron oxides predominantly of the γ-Fe2O3 form with a hydrodynamic diameter ranging from 57-59 nm and strong T2 relaxivity of 164 liters * mmol−1 * S−1 (water, 0.47 T). In rats the particles exhibited a dose-dependent half-life of between 2 and 3 days in the liver at a dose of 20 μmol Fe/kg and a shorter half-life at lower doses. No major side effects were found. In a rat tumor model the tumor-to-liver contrast was markedly improved after i.v. administration of SH U555A. At a dose of 14 μmol Fe/kg the half-maximal contrast-effect was obtained even in nonoptimized T1-weighted spin-echo images. Conclusion: SH U555A is a superparamagnetic MR contrast agent for i.v. administration and has substantial potential for the demarcation of liver tumors.

MR lymphography using iron oxide particles. Detection of lymph node metastases in the VX2 rabbit tumor model.

MR images of the iliac lymph nodes of 25 VX2 carcinoma-bearing rabbits and of 5 tumor-free rabbits were obtained at 1.5 T before and after endolymphatic administration of superparamagnetic iron oxide particles (SPIO) at a dose of 1 μmol Fe per extremity. Imaging results were correlated with histology. In unenhanced images intranodal metastases were not detectable with any of the pulse sequences used and the signal intensities of tumor-free and metastatic lymph nodes did not differ significantly. After administration of the contrast medium, a significant signal loss (p≤0.05) occurred in the healthy lymph node tissue, whereas the signal intensity of lymph node metastases remained unchanged. In SPIO enhanced images, the threshold size for detection of lymph node metastases was 2 mm. Metastatic involvement was detected in 28 of the 30 tumorous lymph nodes with the SE 2 000/15 sequence but in a smaller number of lymph nodes with the sequences SE 500/22 (n = 27) and 2 000/65 (n = 21).

Development of Low-Dose Photon-counting Contrast-enhanced Tomosynthesis with Spectral Imaging

PURPOSE To demonstrate the feasibility of low-dose photon-counting tomosynthesis in combination with a contrast agent (contrast material-enhanced tomographic mammography) for the differentiation of breast cancer. MATERIALS AND METHODS All studies were approved by the institutional review board, and all patients provided written informed consent. A phantom model with wells of iodinated contrast material (3 mg of iodine per milliliter) 1, 2, 5, 10, and 15 mm in diameter was assessed. Nine patients with malignant lesions and one with a high-risk lesion (atypical papilloma) were included (all women; mean age, 60.7 years). A multislit photon-counting tomosynthesis system was utilized (spectral imaging) to produce both low- and high-energy tomographic data (below and above the k edge of iodine, respectively) in a single scan, which allowed for dual-energy visualization of iodine. Images were obtained prior to contrast material administration and 120 and 480 seconds after contrast material administration. Four readers independently assessed the images along with conventional mammograms, ultrasonographic images, and magnetic resonance images. Glandular dose was estimated. RESULTS Contrast agent was visible in the phantom model with simulated spherical tumor diameters as small as 5 mm. The average glandular dose was measured as 0.42 mGy per complete spectral imaging tomosynthesis scan of one breast. Because there were three time points (prior to contrast medium administration and 120 and 480 seconds after contrast medium administration), this resulted in a total dose of 1.26 mGy for the whole procedure in the breast with the abnormality. Seven of 10 cases were categorized as Breast Imaging Reporting and Data System score of 4 or higher by all four readers when reviewing spectral images in combination with mammograms. One lesion near the chest wall was not captured on the spectral image because of a positioning problem. CONCLUSION The use of contrast-enhanced tomographic mammography has been demonstrated successfully in patients with promising diagnostic benefit. Further studies are necessary to fully assess diagnostic sensitivity and specificity.

Intravenous MR lymphography with superparamagnetic iron oxide particles: experimental studies in rats and rabbits

The inter- and intralymphonodal distribution of IV-administered superparamagnetic iron oxide (SPIO) particles as a lymphographic contrast agent for MRI was studied in various animal models in rats and rabbits. In all animals a dosage of 200 μmol Fe/kg was tested. Imaging was done at 1.5 Tesla using proton-density-weighted spin-echo (PD-SE) and T2*-weighted gradient-echo (T2*-GRE) sequences. The time course of signal loss in popliteal lymph nodes of 21 rats was studied before and up to 72 h after IV injection of SPIO. Another 6 rats were dissected 24 h after IV injection of SPIO, all lymph nodes were embedded in agar gel and imaged ex vivo. Time course and pattern of lymph node signal loss was studied in 6 rabbits with reactive lymph node hyperplasia. The visualization of lymph node metastases was studied in 4 VX2 tumor-bearing rabbits. Most pronounced signal loss in lymph nodes was found 24 h after IV injection of SPIO with a decrease of signal in popliteal lymph nodes to 37 ± 15% (9 ± 5%) for rats and 56 ± 10% (16 ± 9%) for rabbits with the PD-SE (T2*-GRE) sequence. Ex vivo examinations of rat lymph nodes and in vivo examinations in rabbits with lymph node hyperplasia demonstrated marked variations in contrast agent accumulation between different lymph node groups. In VX2 tumor-bearing rabbits lymph node metastases could be well delineated in postcontrast MRI if a sufficient amount of contrast agent reached the lymph nodes (2 rabbits). Inhomogeneous signal loss as well as supersaturation impeded correct lymph node assessment (2 rabbits). We conclude that IV MR lymphography using SPIO may be an approach for non invasive tumor staging, but this new technique could be limited by variations in contrast agent distribution between different lymph node groups.