A team of researchers at Massachusetts General Hospital (MGH) has developed a potential alternative to gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI). In his report published in 1945 Radiology the team describes experiments showing in a primate model that the manganese-based agent Mn-PyC3A produces a contrast enhancement of blood vessels equivalent to that of gadolinium-based agents, which involve significant risks to the health of certain patients.
"About 40% of MRI procedures use a contrast agent to produce a signal capable of detecting cancer, diagnosing aneurysms or arterial narrowing, or identifying the region of the heart damaged by a heart attack, "says Peter Caravan. the Martinos Center for Biomedical Imaging and co-director of the Institute for Imaging Innovation at MGH, corresponding author of the document Radiology . "All current FDA-approved contrast agents contain gadolinium, which was associated in 2006 with a devastating disease called nephrogenic systemic fibrosis in patients with impaired renal function.We estimate that about 2 million 39 Contrast exams are not performed in the United States each year due to the inability to use BCAGs in patients with poor kidney function. "
More recent reports of gadolinium deposits in the brain and other patient organs have added to GBCA's safety concerns, prompting the US FDA to reiterate the need for caution and restraint in 39, use of agents and the European Medical Association. withdraw from the market three of the seven already approved agents and restrict the use of other agents earlier this year.
Caravan and his colleague Eric Gale, PhD, of the Martinos Center developed their Mn-PyC3A manganese agent based on two properties of the element: its ability to produce an MR signal comparable to that of the GBCA and the fact that - unlike gadolinium, which is not naturally present in the human body, manganese is an essential element and the intake of small amounts is necessary for the vital functions of the body. The body has natural mechanisms to treat and excrete excess manganese, but any gadolinium released by the GBCA is likely to be retained indefinitely in the body.
Previous studies conducted by the team on mouse models showed that Mn-PyC3A was very resistant to the release of manganese ions; that it has provided a good improvement of blood vessels, liver and kidneys; More than 99 percent was excreted by the body within 24 hours and eliminated by both the liver and the kidneys, reducing the likelihood of prolonged retention in subjects with poor kidney function . For the present study, the researchers compared the use of Mn-PyC3A to a commonly used GBCA in a baboon model.
Each animal underwent two magnetic resonance imaging sessions, one with Mn-PyC3A and one with GBCA. The scans were performed under identical conditions - the scanner used, the assays and the imaging protocols were the same as those used for human patients - and the improved images of the main arteries, kidneys, livers and specific muscles produced by the two agents were comparable. As in the study in mice, Mn-PyC3A was rapidly excreted by clearance of the kidneys and liver, and there was no evidence of free manganese release.
Gale explains: "Although we have not tested it here, we believe that the elimination of Mn-PyC3A in patients with kidney disease and the lack of Contrast retention is an effective mechanism for elimination via the hepatic route.Our next steps are the manufacture of Mn-PyC3A on a larger scale and the realization of additional preclinical safety studies before we can start the tests at human patients. "
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