Development of an ErbB-overexpressing A-431 optical reporting tumor xenograft model to assess targeted photodynamic therapy regimens.

To better assess the efficacy of erbB-targeted therapies, it would help to have optical reporting human tumor xenograft models that abundantly express erbB receptors. A-431 cells have frequently been used in erbB1-targeting studies, but a well-characterized optical reporting version of the cell line has not been readily available. In this study, optical reporting A-431 clones were developed that express both a fluorescent protein reporter (green, GFP; or red, RFP) and a bioluminescent reporter, firefly luciferase. Reporter genes were transduced into cells using commercial lentiviral vectors, and clonal selection was carried out using a series of procedures. A number of clones were isolated for further characterization. A GFP/luciferase clone, A-431/D4, and an RFP/luciferase clone, A-431/G4, were obtained that exhibit erbB1 expression levels and tumor growth kinetics similar to the parental cells. To demonstrate the utility of the optical reporting clones, A-431/G4 tumors were grown subcutaneously in nude mice and treated with vascular-targeted photodynamic therapy (PDT), which targets the angiogenic consequences of erbB signaling. The A-431/G4 tumor model permitted highly sensitive longitudinal monitoring of PDT treatment response using optical imaging. A-431/D4 and A-431/G4 optical reporting tumor models should also prove useful for assessing therapies that directly target the erbB1 receptor.

Assessment of sequential enhancement patterns of focal nodular hyperplasia and hepatocellular carcinoma on mangafodipir trisodium enhanced MR imaging.

RATIONALE AND OBJECTIVES: Sequential contrast changes of mangafodipir trisodium (Mn-DPDP)-enhanced magnetic resonance imaging (MRI) were evaluated in the differentiation of focal nodular hyperplasias (FNH) and hepatocellular carcinomas (HCC). METHODS: Patients with FNH (n = 16) or HCC (n = 12) underwent MRI: T2-weighted fast spin echo before and T1-weighted gradient echo before and 1, 4, 14, and 22 hours after 5 micromol/kg Mn-DPDP. Homogeneity of enhancement and delineation of fibrous scars of FNHs were assessed qualitatively. Lesion-to-liver contrast changes of FNHs and HCCs were compared quantitatively (Mann-Whitney U). RESULTS: Mn-DPDP improved detection of characteristic scars of FNHs from 50% before to 90% after contrast agent. Apart from fibrous tissue enhancement of FNHs was mostly homogeneous (90%). Time-dependent contrast changes were up to 20 times higher (after 4 hours) for FNHs than HCCs (P < 0.0001). CONCLUSIONS: Mn-DPDP-enhanced MRI helps to delineate characteristic morphologic features of FNHs and can provide quantitative data differentiating FNH and HCC.

3D CT modeling of hepatic vessel architecture and volume calculation in living donated liver transplantation.

The aim of this study was to evaluate a software tool for non-invasive preoperative volumetric assessment of potential donors in living donated liver transplantation (LDLT). Biphasic helical CT was performed in 56 potential donors. Data sets were post-processed using a non-commercial software tool for segmentation, volumetric analysis and visualisation of liver segments. Semi-automatic definition of liver margins allowed the segmentation of parenchyma. Hepatic vessels were delineated using a region-growing algorithm with automatically determined thresholds. Volumes and shapes of liver segments were calculated automatically based on individual portal-venous branches. Results were visualised three-dimensionally and statistically compared with conventional volumetry and the intraoperative findings in 27 transplanted cases. Image processing was easy to perform within 23 min. Of the 56 potential donors, 27 were excluded from LDLT because of inappropriate liver parenchyma or vascular architecture. Two recipients were not transplanted due to poor clinical conditions. In the 27 transplanted cases, preoperatively visualised vessels were confirmed, and only one undetected accessory hepatic vein was revealed. Calculated graft volumes were 1110 +/- 180 ml for right lobes, 820 ml for the left lobe and 270 +/- 30 ml for segments II+III. The calculated volumes and intraoperatively measured graft volumes correlated significantly. No significant differences between the presented automatic volumetry and the conventional volumetry were observed. A novel image processing technique was evaluated which allows a semi-automatic volume calculation and 3D visualisation of the different liver segments.