Antonina Bergman

An iodinated lipid emulsion for CT of the liver : Comparison with iohexol in the detection of experimental hepatic metastases

Purpose: The iodinated hepatocyte-specific lipid emulsion FP 736-03 for CT of the liver was tested against the conventional water-soluble contrast agent iohexol. Material and Methods: A nude rat model of experimental multiple hepatic metastases from a human colonic cancer was used. The animals were examined 3 weeks after intraportal tumor cell injection. Native examination, and iohexol- and FP-736-03-enhanced CT were performed. The detection rate was determined on a lesion-by-lesion basis. Metastatic diameters measured on CT images were compared with corresponding macroscopic serial liver specimens. Results: In a lesion-by-lesion analysis of 140 metastases, the detection rates for 2 viewers were 16.4% and 30.7% for native examination, 12.9% and 17.9% for iohexol-enhanced CT, and 53.6% and 72.1 % for FP-736-03-enhanced CT, respectively. The detection rates tended to increase with lesion diameter. Conclusion: The hepatocyte-specific contrast medium FP 736-03 improved the detection rate significantly in comparison with both native and iohexol-enhanced CT.

Detection and characterisation of renal lesions by multiphasic helical CT.

Purpose: The fast helical CT technique allows examination of the kidneys during different phases of contrast medium enhancement. However, every additional phase increases the radiation dosage to the patients. We investigated the detection rate and characterisation of renal lesions during different phases and evaluated them separately, and considered the possibility of excluding phases without loss of important information. Material and Methods: Sixty patients who underwent contrast-enhanced multiphasic renal helical CT examination were included. Every CT phase was evaluated separately. The number of lesions and the characteristics of the lesions were noted and all lesions were viewed together. Results: A total of 153 cysts and 17 solid lesions were detected. The largest and an equal number of cysts (142/143) was detected in the nephrographic and excretory phases. However, the nephrographic phase detected more cortical cysts and the excretory phase detected more sinus cysts. All solid lesions were detected in all phases. Renal parenchymal tumours were best characterised in the cortical phase and angiomyolipomas in the native phase. Conclusion: The cortical phase was best for characterisation of renal parenchymal tumours. The nephrographic and excretory phases were best in detecting and characterising renal cysts. The nephrographic phase was the phase giving the least diagnostic information.

CT with the hepatocyte-specific contrast medium fp 736-04 in an experimental model of liver steatosis

Purpose: to investigate whether liver uptake of the iodinated hepatocyte-specific lipid emulsion FP 736-04 is altered by fatty infiltration of the liver. Material and Methods: Fatty infiltration of the liver was induced in female Sprague Dawley rats by an intraperitoneal injection of L-ethionine preceded by 15 h of food withdrawal. CT of the liver was performed before and 24 h after the administration of L-ethionine and, in addition at the latter time point, after an i.v. injection of 1.0 ml/kg b.w. of FP 736-04. A control group was subjected to the same CT examination protocol. Results: Intraperitoneal administration of L-ethionine caused liver steatosis, as established by liver triglyceride analysis, leading to a significant decrease in the liver attenuation, from 69.2±2.4 to 27.8±12.0 HU. the uptake of FP 736-04 by the fatty liver was significantly reduced, yielding a maximum enhancement of 22.3±7.9 HU as compared to a value of 32.3±5.0 HU in the control group. Conclusion: Enhancement by FP 736-04 was reduced in the steatotic liver compared with the normal liver. It remains to be established whether this degree of enhancement is sufficient for reliable lesion detection.

CT of experimental hepatoma using the hepatocyte-specific lipid emulsion fp 736-03

Purpose: the aim of the study was to investigate whether moderately to well differentiated hepatocellular carcinomas (HCC) possess the same ability to take up a new lipid emulsion contrast medium, FP 736-03, as do hepatocytes. Material and Methods: A rat model of an experimental HCC was used. CT was performed before and after an i.v. bolus injection of 1.0 ml FP 736-03/kg b.w. Attenuation values of normal liver parenchyma and tumour tissue were measured over time. Results: the contrast medium was taken up by the normal liver parenchyma but not by the tumour tissue for which the attenuation remained virtually constant over the observation period. Conclusion: the study demonstrated that FP 736-03 was not taken up by the HCC, thus producing a high lesion-to-liver contrast.

CT with different doses of the hepatocyte-specific contrast medium FP 736-03. Evaluation in a nude-rat model of experimental metastases.

Purpose: to study the dose-response relationship in FP 736-03 (48 mg I/ml), a hepatocyte-specific contrast medium for CT of the liver Material and Methods: A nude-rat model of experimental hepatic metastases was used. CT of the liver was performed before and after i.v. injection of FP 736-03 at 4 different doses: 0.25, 0.5, 1.0 and 2.0 ml/kg b.w. Attenuation in the normal liver parenchyma and in the metastases was measured and plotted as a function of time Results: the enhancement of the normal liver parenchyma increased in the dose range studied. No increase was found in the metastases; the attenuation here remained constant during the observation period. the maximum enhancement values at doses of 0.25, 0.5, 1.0 and 2.0 ml/kg b.w. were (mean ± SD) 13.5±2.7, 30.1±4.2, 33.2±4.5 and 59.7±13.1 HU respectively

Efficacy of the hepatocyte-specific contrast medium FP 736-04 for CT in two models of experimental diffuse liver disease.

Efficacy of the hepatocyte-specific contrast medium FP 736-04 for CT in two models of experimental diffuse liver disease

Contrast enhancement of the liver in healthy male volunteers following intravenous administration of FP 736-04

Computed tomography (CT) is a widely available and easily reproducible technique which is accepted both by the radiologists and clinicians for imaging of hepatic masses. Using CT, delineation of space occupying lesions in the liver is highly dependent on the liver-to-lesion attenuation difference (1). Water-soluble contrast media (CM), however, alter this liver-to-lesion attenuation ratio in a nonselective manner. A liver-specific CM is expected to offer important advantages over the currently used conventional agents. Such a CM, enhancing normal liver parenchyma selectively, and thus not accumulating in tumor tissue, would facilitate lesion depiction and detection (29). Unlike previous organ-specific CM, which have relied on accumulation in the cells of the reticular endothelial system (RES) (6,7,10), the preparation FP 736-04 examined in the present study is hepatocyte-specific. The aim of this study was to document contrast enhancement of normal liver at different dosages. Secondary objectiveswere to document pharmacokinetics and safety.

Relationship between contrast enhancement and diagnostic accuracy with the liver-specific CT contrast medium FP 736-04 in an experimental model of liver metastases

RATIONALE AND OBJECTIVES The authors sought to establish the optimal level of liver enhancement at computed tomography (CT) with a hepatocyte-specific contrast medium in an experimental model of liver metastases. MATERIALS AND METHODS Anesthetized nude rats (n = 18) injected intraportally with cells from human colonic adenocarcinoma and Sprague-Dawley rats (n = 11) without metastases were used. A fractional intravenous infusion of contrast material was given in escalating doses up to a total of 4.0 mL per kilogram of body weight. Mean attenuation of the liver was calculated for each accumulated dose, and the overall detection rate was determined on a lesion-by-lesion basis. Sensitivity, specificity, and positive and negative predictive values were also established for each dose. RESULTS Liver metastases were diagnosed with increasing reliability for enhancement values of up to 30.0 HU +/- 5.2 (mean +/- standard deviation), which corresponded to a dose of 0.5 mL/kg. CONCLUSION In this model, optimal reliability in the diagnosis of liver metastases with CT was achieved at an enhancement value of approximately 30 HU.

The efficacy of fp 736-04 in experimental liver cirrhosis:

Purpose: to determine whether the uptake of FP 736-04, a hepatocyte-specific CT contrast agent, is influenced by cirrhotic changes in the liver Material and Methods: Liver cirrhosis was induced by bile duct ligation (BDL) in Sprague-Dawley rats. Seventy-four animals were divided into three groups comprising: rats with acute BDL; rats with chronic BDL; and normal controls. CT was performed after i.v. infusion of FP 736-04 or saline at a dose of 2 ml/kg b.w., and the mean attenuation in the liver and spleen was measured. the livers from the chronic BDL group were taken for histopathological examination and the extent of the disease was graded according to an arbitrary scale Results and Conclusion: There was a significant reduction of the native liver attenuation in both chronic and acute BDL groups as compared with the normal controls. FP 736-04 was taken up by the liver parenchyma with a similar degree of enhancement in all three groups

Detecting experimental liver metastases at CT with the hepatocyte-specific contrast medium FP 736-03.

Purpose: To evaluate the detection of experimental hepatic metastases at CT with the hepatocyte-specific contrast medium FP 736-03. Material and Methods: A nude-rat model of experimental multiple hepatic metastases from a human colonic cancer was used. Three weeks after intraportal tumour cell injection, the CT examination was performed before and after i.v. injection of FP 736-03 at a dose of 0.5 ml/kg b.w. Results: The overall detection rate was determined in a lesion-by-lesion analysis of 87 metastases. Irrespective of metastatic size, the mean detection rate for two viewers was significantly higher at the FP-736-03-enhanced examination (59%) than at the unenhanced CT examination (16%). Conclusion: The detection rate increased with the i.v. administration of FP 736-03 at a dose of 0.5 ml/kg b.w. compared with that at unenhanced examination.