Carboxymethyldextran-A2-Gd-DOTA enhancement patterns in the abdomen and pelvis in an animal model

Abstract

The aim of this study was to assess MR signal enhancement patterns of carboxymethyldextran (CMD)-A2-Gd-DOTA, a new macromolecular contrast agent, in the abdomen and pelvis of New Zealand white rabbits. Nine New Zealand white rabbits underwent MRI before and following injection of 0.05 mmol/kg body weight (bw) CMD-A2-Gd-DOTA (52.1 kDa), using turbo FLASH-, dynamic FLASH 60 degrees-, T1- and T2-weighted spin-echo and turbo spin-echo sequences up to 10 days p.i. Changes in blood and tissue signal intensities (deltaSI) and relaxation rates (deltaR1) were calculated. Differences between pre- and post-contrast MRI data were compared using the Scheffé test. CMD-A2-Gd-DOTA demonstrated significant blood-pool enhancement and significant tissue enhancement on T1-weighted images, whereas no significant signal changes were observed on T2-weighted images (P < 0.05). Kidney parenchyma, pelvis and bladder demonstrated a subsequent enhancement, resembling renal elimination of the majority of the contrast agent. Liver parenchyma demonstrated a slow, delayed decay of the contrast enhancement due to storage and biodegradation of larger subfractions of the contrast agent. All tissue signal intensities were back to baseline 10 days p.i. CMD-A2-Gd-DOTA is a new macromolecular contrast agent with blood-pool effect, significant signal enhancement of abdominal organs and pelvic bone marrow, partial storage in the liver and baseline tissue signal intensities by 10 days p.i.

Magnetic resonance characterization of tumor microvessels in experimental breast tumors using a slow clearance blood pool contrast agent (carboxymethyldextran-A2-Gd-DOTA) with histopathological correlation

“…CMD-A2-Gd-DOTA was well tolerated in all anesthetized rats. This observation is in agreement with previous studies [15,34,39] that showed no toxic effects at a dose of 0.05 mmol. The hypothesis of the present study was that CMD-A2-Gd-DOTA can be used for characterization of tumor microvessels.…”

“…Another potential clinical application is MR angiography [36][37][38]. Following its intravenous administration at a dose of 0.05 mmol Gd/kg body weight in an experimental rabbit model CMD-A2-Gd-DOTA demonstrated significant signal enhancement of abdominal organs and pelvic bone marrow, partial storage in the liver, and return to baseline signal intensities after 10 days postinjection [39]. To our knowledge, CMD-A2-Gd-DOTA has not been previously tested for its potential to characterize tumor microvessels.…”

“…Since the prototype macromolecular contrast agent albumin-(Gd-DTPA) 30 , with a molecular weight of 92 kDa, seems to be unsuitable for clinical use because its renal excretion is incomplete and slow, CMD-A2-Gd-DOTA may offer a compromise between the required renal elimination and the blood pool properties. The reported prolonged retention [15,39] of CMD-A2-Gd-DOTA in the liver could indicate also a minor component of hepatic metabolism and fecal excretion. CMD-A2-Gd-DOTA was well tolerated in all anesthetized rats.…”

Tracking Cell Transplants in Femoral Osteonecrosis with Magnetic Resonance Imaging: A Proof-of-Concept Study in Patients

“…Our imaging test can track the location, estimate the quantity and provide information about the phagocytic activity of bone marrow cells. For example, we previously noted that normal bone marrow cells of young patients take up more iron compared to bone marrow cells of older patients (42,43). Our imaging test cannot determine the efficacy of the transplanted cells to regenerate bone.…”

How PET/MR Can Add Value for Children with Cancer

“…Whole body MR has been used for screening patients with cancer predisposition syndromes, cancer staging of patients with hereditary increased radiosensitivity, staging of benign disease such as Langerhans Cell Histiocytosis, staging of non 18 F-FDG-avid tumors and patients without access to an 18 F-FDG PET/CT scan [40, 39, 41]. Since most tumors have a higher cell density than normal organs, the diffusional motion of water protons is more restricted in tumors and displayed by an increased signal intensity on diffusion weighted MR images [8, 42, 43].…”