Peter F. Hahn

BACKGROUND: Accurate detection of lymph-node metastases in prostate cancer is an essential component of the approach to treatment. We investigated whether highly lymphotropic superparamagnetic nanoparticles, which gain access to lymph nodes by means of interstitial-lymphatic fluid transport, could be used in conjunction with high-resolution magnetic resonance imaging (MRI) to reveal small nodal metastases. METHODS: Eighty patients with presurgical clinical stage T1, T2, or T3 prostate cancer who underwent surgical lymph-node resection or biopsy were enrolled. All patients were examined by MRI before and 24 hours after the intravenous administration of lymphotropic superparamagnetic nanoparticles (2.6 mg of iron per kilogram of body weight). The imaging results were correlated with histopathological findings. RESULTS: Of the 334 lymph nodes that underwent resection or biopsy, 63 (18.9 percent) from 33 patients (41 percent) had histopathologically detected metastases. Of these 63 nodes, 45 (71.4 percent) did not fulfill the usual imaging criteria for malignancy. MRI with lymphotropic superparamagnetic nanoparticles correctly identified all patients with nodal metastases, and a node-by-node analysis had a significantly higher sensitivity than conventional MRI (90.5 percent vs. 35.4 percent, P<0.001) or nomograms. CONCLUSIONS: High-resolution MRI with magnetic nanoparticles allows the detection of small and otherwise undetectable lymph-node metastases in patients with prostate cancer.

Superparamagnetic iron oxide (ferrite) particles were evaluated as a contrast agent for magnetic resonance (MR) imaging. In this pilot study, doses ranging from 10 to 50 mumol/kg were administered intravenously to 15 patients. Ferrite-enhanced images of the liver obtained with standard pulse sequence techniques significantly increased the number of hepatic lesions detected (P less than .01) and reduced the threshold size for detection to 3 mm (P less than .01). The improved clinical performance of ferrite-enhanced images correlated with significant increases in measured contrast-to-noise ratios (P less than .01). Degradation of superparamagnetic activity and/or clearance of ferrite from the liver was demonstrated as early as 12 hours after injection, suggesting that the lack of chronic toxicity observed in animal studies may be reproduced in humans. These initial clinical results appear to confirm extensive preclinical data indicating that ferrite administered at a dose of 20 mumol/kg has the potential to significantly improve the performance of abdominal MR imaging.

PURPOSE: To determine whether computed tomographic (CT) scans and attenuation measurements on contrast material-enhanced and nonenhanced CT scans could be used to characterize adrenal masses, in particular, to characterize these lesions by using adrenal washout characteristics at contrast-enhanced CT. MATERIALS AND METHODS: Eighty-six patients (49 men, 37 women; age range, 29-86 years; mean age, 72 years) with 101 adrenal lesions depicted at contrast-enhanced CT underwent delayed (mean, 9 minutes) enhanced scanning. Seventy-eight patients also underwent nonenhanced CT. Mean diameter of the benign lesions was 2.1 cm (range, 1.0-4.2 cm); mean diameter of the malignant lesions was 2.3 cm (range, 1.0-4.1 cm). Region-of-interest measurements were obtained at nonenhanced, dynamic enhanced, and delayed enhanced CT and were used to calculate a relative percentage washout as follows: 1 - (Hounsfield unit measurement on delayed image / Hounsfield unit measurement on dynamic image) x 100%. RESULTS: Ninety-nine of 101 lesions were correctly characterized as benign or malignant with a relative percentage washout threshold of 50% on delayed scans; benign lesions demonstrated more than 50% washout; and malignant lesions, less than 50% washout. Two benign lesions demonstrating less than 50% washout were characterized as benign by using conventional CT. CONCLUSION: Calculation of relative percentage washout on dynamic and delayed enhanced CT scans may lead to a highly specific test for adrenal lesion characterization, reduce the need for, and possibly obviate, follow-up imaging or biopsy.

Hepatobiliary-specific contrast agents are one of several classes of contrast agents available for magnetic resonance (MR) imaging of the liver. These agents are taken up by functioning hepatocytes and excreted in the bile, and their paramagnetic properties cause shortening of the longitudinal relaxation time (T1) of the liver and biliary tree. The three contrast agents that have been developed are mangafodipir trisodium (Mn-DPDP), gadobenate dimeglumine (Gd-BOPTA), and gadoxetic acid (Gd-EOB-DTPA). These three MR contrast agents vary in mode of administration and dose, mechanism of cellular uptake, degree of excretion through the biliary pathway, and imaging characteristics. In the liver, hepatobiliary-specific agents can be used to improve lesion detection, to characterize lesions as hepatocellular or nonhepatocellular, and to specifically characterize some hepatocellular lesions, notably focal nodular hyperplasia. Biliary excretion of these agents can be used to evaluate the anatomic structure and function of the biliary tree. In the future, hepatobiliary-specific contrast agents may have wider applications, such as grading of cirrhosis and quantification of liver function.