Detection and characterization of primary liver cancer in rats by MS‐264‐enhanced MRI

Abstract

A new MR contrast agent, MS-264 (Gd(1RS)-1-(p-butylbenzyl)-DTPA), was developed to achieve hepatobiliary specificity and its potential evaluated for detecting and characterizing liver tumors in rats with chemically induced hepatocellular carcinoma (HCC). In seven rats with 66 HCC lesions, enhancements of different abdominal organs and tumors were compared on T1-weighted images after intravenous administration of Gd-DTPA (0.3 mmol/kg) and MS-264 (0.05 mmol/kg). MR images were correlated with postmortem microangiographic and histological findings. An overall enhancement of different organs, which normalized within 24 h, was observed after Gd-DTPA and MS-264 injection. MS-264 caused a higher relative enhancement (RE) in liver (60%), compared with that of Gd-DTPA (40%), which resulted in a prompt negative contrast enhancement in 59 of 66 HCCs. All were moderately to poorly differentiated (Grades II-IV) tumors. Six of these 59 negative contrast-enhancing lesions showed a positively enhanced peritumoral rim, which corresponded histologically to malignant infiltration (n = 2) or compression (n = 4). On the other hand, six well differentiated HCCs showed prolonged positive enhancement. However, one well differentiated HCC was not positively enhanced by MS-264, probably due to poor access of the agent to the lesion. In comparison to that of the precontrast images, enhancement with Gd-DTPA and MS-264 increased the number of detected lesions by 22 and 42%, respectively. In this animal study, MS-264 proved to be useful in detection and characterization of primary liver cancers.

Tumor models and specific contrast agents for small animal imaging in oncology

“…Such TCE never appears with nonspecific CAs such as Gd-DTPA. After investigating over hundred accumulated animal tumors, we were the first to publish such findings in order to draw public attentions to their potential for differential diagnosis of focal liver lesions [11][12][13]15]. However, by studying only 31 patients without positive TCE encountered, Vogl et al in their first clinical report attempted to challenge our initial findings and concluded that similar to Gd-DTPA, Gd-EOB-DTPA could not provide ''differential diagnostic information" [64].…”

“…MRI prior to I but overnight post Mn-DPDP injection in J, normal liver lobes (NL) showed contrast clearance but CE persisted in the ligated lobes (BL), supporting the proposed mechanisms for positive TCE and rim-CE with Mn-DPDP. normal hepatocytes and liver tumors of various origins and grades [11][12][13]15]. Comparing to Mn-DPDP, these hepatobiliary CAs also showed positive, negative and rim TCE but in quite dissimilar tumor differentiation spectra (Table 3).…”

“…Since both types of hepatobiliary CAs are now commercially available, if we can afford, consecutive use of them in the same patients of liver masses may further narrowing the likelihood of histopathological diagnoses by merely noninvasive CE-MRI [13,15]. Such a virtual biopsy approach may not only benefit therapeutic decision-making but also assist prognosis estimation (Table 4).…”

Gadolinium Meets Medicinal Chemistry: MRI Contrast Agent Development

“…Liver imaging of rats with chemically induced hepatocellular carcinoma (HCC) resulted in a higher relative enhancement of normal liver tissue as compared with Gd-DTPA alone or no contrast. Of the 66 HCCs detected, 59 showed negative contrast enhancement and 6 positive enhancement [22].…”

Trends in Contrast Media

“…Chelates with lipophilic components were investigated as potentially liver-specific compounds (VITTADINI et al 1988;WEINMANN et al 1991;SCHUHMANN-GIAMPIERI et al 1992;PETRE et al 1995;RUNGE and WELLS 1995). All hepatocytespecific agents are ionic metal chelates and, unlike many other hepatotropic compounds, display a relatively pronounced hydrophilicity.…”