Advocating the Development of Next-Generation High-Relaxivity Gadolinium Chelates for Clinical Magnetic Resonance.

Runge, Val Murray; Heverhagen, Johannes (2018). Advocating the Development of Next-Generation High-Relaxivity Gadolinium Chelates for Clinical Magnetic Resonance. Investigative radiology, 53(7), pp. 381-389. Lippincott Williams & Wilkins 10.1097/RLI.0000000000000454

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The question of improved relaxivity, and potential efficacy therein, for a next-generation of magnetic resonance gadolinium chelates with extracellular distribution and renal excretion, which could also be viewed from the perspective of dose, is addressed on the basis of historical development, animal experimentation, and human trials. There was no systematic evaluation that preceded the choice of 0.1 mmol/kg as the standard dose for human imaging with the gadolinium chelates. In part, this dose was chosen owing to bloodwork abnormalities seen in phase I and phase II studies. Animal investigations and early clinical trials demonstrated improved lesion detectability at higher doses in the brain, liver, and heart. By designing an agent with substantially improved relaxivity, higher enhancement equivalent to that provided with the conventional gadolinium agents at high dose could be achieved, translating to improved diagnosis and, thus, clinical care. Implicit in the development of such high-relaxivity agents would be stability equivalent to or exceeding that of the currently approved macrocyclic agents, given current concern regarding dechelation and gadolinium deposition in the brain, skin, and bone with the linear agents that were initially approved. Development of such next-generation agents with a substantial improvement in relaxivity, in comparison with the current group of approved agents, with a 2-fold increase likely achievable, could lead to improved lesion enhancement, characterization, diagnosis, and, thus, clinical efficacy.

Item Type:

Journal Article (Review Article)

Division/Institute:

04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Institute of Diagnostic, Interventional and Paediatric Radiology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Radiologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Radiologie

UniBE Contributor:

Runge, Val Murray and Heverhagen, Johannes

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0020-9996

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Nicole Rösch

Date Deposited:

23 Apr 2018 08:59

Last Modified:

18 Feb 2019 02:30

Publisher DOI:

10.1097/RLI.0000000000000454

PubMed ID:

29462023

BORIS DOI:

10.7892/boris.113303

URI:

https://boris.unibe.ch/id/eprint/113303

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