Gadopentetate dimeglumine Other names: Gadopentetic acid Gd-DTPA

Gadopentetic acid is a paramagnetic contrast agent for magnetic resonance imaging. The contrast-enhancing effect is mediated by the di-N-methylglucamine salt of gadopentetic acid, dimeglumine – the gadolinium complex of pentetic acid (diethylene triamine pentaacetic acid = DTPA). When a suitable scanning sequence (e.g. T₁-weighted spin-echo technique) is used in proton magnetic resonance imaging, the gadolinium ion-induced shortening of the spin-lattice relaxation time of excited atomic nuclei leads to an increase of the signal intensity and, hence, to an increase of the image contrast of certain tissues.

Gadopentetic acid, dimeglumine is a highly paramagnetic compound which leads to distinct shortening of relaxation times, even in low concentrations. The paramagnetic efficacy, the relaxivity (determined from the influence on the spin-lattice relaxation time of protons) is 3.67 in water and about 4.95 l/mmol/sec in plasma, and displays only slight dependency on the strength of the magnetic field.

The concentration of gadopentetic acid corresponds to 1/250 of the concentration used for i.v. administration. This concentration is sufficient to allow adequate imaging efficacy even after further dilution with joint effusion. If the joint cavity is filled with gadolinium-containing fluid, the signal in the cavity increases on use of T₁-weighted sequences, i.e. it becomes bright and contrasts clearly with all structures with a weak or intermediate signal (i.e. all intraarticular structures: hyaline and fibrous cartilage, all ligaments, tendons and the joint capsule). While normal, or even increased, joint fluid does not differ in its signal behaviour in T₁-weighted images from all the other anatomical structures apart from fibrocartilage, the intraarticular administration of gadopentetic acid leads to distinctly improved contrast situations.

DTPA forms a firm complex with the paramagnetic gadolinium ion with extremely high in vivo and in vitro stability (log K = 22-23). The dimeglumine salt of gadopentetic acid, dimeglumine is a highly water-soluble, extremely hydrophilic compound with a distribution coefficient between n-butanol and buffer at pH 7.6 of about 0.0001. The substance does not display any particular protein binding or inhibitory interaction with enzymes (e.g. myocardial Na and K ATPase). Gadopentetic acid does not activate the complement system and, therefore, probably has a very low potential for inducing anaphylactoid reactions.

The pharmacokinetic properties of gadopentetic acid, dimeglumine have been extensively studied after intravenous and oral administration in doses exceeding the amount injected intraarticularly.

After intraarticular injection the compound distributes in the synovial fluid and diffuses into the interstitial space. Marginal uptake into the cartilage is completely reversible.

After distribution in the extracellular space primarily through diffusion controlled processes, the gadopentetic acid, dimeglumine is eliminated unmetabolised via the kidneys by glomerular filtration.

Gadopentetic acid, dimeglumine salt is a linear GdCA. Studies have shown that after exposure to GdCAs given intravenously at significantly higher doses than intra-articular products gadolinium is retained in the body. This includes retention in the brain and in other tissues and organs. With the linear GdCAs this can cause dose-dependent increases in T1-weighted signal intensity in the brain, particularly in the dentate nucleus, globus pallidus, and thalamus. Signal intensity increases and non-clinical data show that gadolinium is released from linear GdCAs.

Non-clinical data reveal no special hazard for humans based on conventional studies of systemic toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction and contact sensitising potential.

Local tolerance: Experimental local tolerance studies with gadopentetic acid, dimeglumine (at a concentration of 500 mmol/l) following single subcutaneous and intramuscular administration in animals indicated that slight local intolerance reactions could occur at the injection site after inadvertent administration.