The Issue of Gadolinium Retained in Tissues: Insights on the Role of Metal Complex Stability by Comparing Metal Uptake in Murine Tissues Upon the Concomitant Administration of Lanthanum- and Gadolinium-Diethylentriamminopentaacetate.

Title The Issue of Gadolinium Retained in Tissues: Insights on the Role of Metal Complex Stability by Comparing Metal Uptake in Murine Tissues Upon the Concomitant Administration of Lanthanum- and Gadolinium-Diethylentriamminopentaacetate.
Authors E. Di Gregorio; G. Ferrauto; C. Furlan; S. Lanzardo; R. Nuzzi; E. Gianolio; S. Aime
Journal Invest Radiol
DOI 10.1097/RLI.0000000000000423
Abstract

OBJECTIVES: The aim of the study was to explore the role of the stability of metal complexes in the processes that lead to the metal retention in the brain and other tissues of mice administered with lanthanides-based contrast agents. This issue was tackled by the simultaneous injection of gadolinium (Gd)-diethylentriamminopentaacetate (DTPA) and lanthanum-DTPA, which have the same charge and structure but differ in their thermodynamic stability by 3 orders of magnitude.

MATERIALS AND METHODS: A total of 20 healthy BALB/c mice were administered by a single intravenous injection with a dose consisting of 0.6 mmol La-DTPA/kg and 0.6 mmol Gd-DTPA/kg. Then the animals were killed at different time points: 4, 24, 48, and 96 hours (5 mice each group).In an additional protocol, 5 mice were administered with 9 doses of 0.3 mmol La-DTPA/kg and 0.3 mmol of Gd-DTPA/kg every 2 days over a period of 3 weeks. The sacrifice time was set to 3 weeks after the last administration. After sacrifice, the Gd and La content in liver, spleen, kidney, muscle, cerebrum, cerebellum, bone, eye, skin, blood, and urine was determined by inductively coupled plasma-mass spectrometry.

RESULTS: A general decrease in the content of both the lanthanides was observed upon delaying the sacrifice time. At relatively short times after the injection (up to 96 hours), in the spleen, kidney, muscle, skin, and eye, almost the same content of La and Gd was detected, whereas in the cerebrum, cerebellum, bones, and liver, the amount of retained La decreased much slower than that of Gd, yielding a progressive increase in La/Gd ratio. The amount of retained La in the various tissues 21 days after the last of 9 administrations of La-DTPA and Gd-DTPA was always significantly higher than that of Gd. The concentration of both La and Gd decreased rapidly both in blood and in urine samples.

DISCUSSION: The departure from the 1:1 ratio in the amounts of La and Gd determined in the investigated tissues has been used to gain information on the role of the complex stability and "wash-out" kinetics. The behavior of the less s` La-DTPA highlights processes occurring for Gd-DTPA at a slower rate.The herein obtained results support the view that most of the La/Gd retained in the brain arises from the intact chelate that has extravasated immediately after the intravenous administration. Long-term deposition of metal ions from internal reservoirs seems particularly relevant for liver and spleen.

Citation E. Di Gregorio; G. Ferrauto; C. Furlan; S. Lanzardo; R. Nuzzi; E. Gianolio; S. Aime.The Issue of Gadolinium Retained in Tissues: Insights on the Role of Metal Complex Stability by Comparing Metal Uptake in Murine Tissues Upon the Concomitant Administration of Lanthanum- and Gadolinium-Diethylentriamminopentaacetate.. Invest Radiol. 2018;53(3):167172. doi:10.1097/RLI.0000000000000423

Related Elements

Gadolinium

See more Gadolinium products. Gadolinium (atomic symbol: Gd, atomic number: 64) is a Block F, Group 3, Period 6 element with an atomic radius of 157.25. Gadolinium Bohr ModelThe number of electrons in each of Gadolinium's shells is [2, 8, 18, 25, 9, 2] and its electron configuration is [Xe] 4f7 5d1 6s2. The gadolinium atom has a radius of 180 pm and a Van der Waals radius of 237 pm. Gadolinium was discovered by Jean Charles Galissard de Marignac in 1880 and first isolated by Lecoq de Boisbaudran in 1886. In its elemental form, gadolinium has a silvery-white appearance. Gadolinium is a rare earth or lanthanide element that possesses unique properties advantageous to specialized applications such as semiconductor fabrication and nuclear reactor shielding. Elemental Gadolinium PictureIt is utilized for both its high magnetic moment (7.94μ B) and in phosphors and scintillator crystals. When complexed with EDTA ligands, it is used as an injectable contrast agent for MRIs. The element is named after the Finnish chemist and geologist Johan Gadolin.

Lanthanum

See more Lanthanum products. Lanthanum (atomic symbol: La, atomic number: 57) is a Block F, Group 3, Period 6 element with an atomic weight of 138.90547. Lanthanum Bohr ModelThe number of electrons in each of lanthanum's shells is [2, 8, 18, 18, 9, 2] and its electron configuration is [Xe] 5d1 6s2. The lanthanum atom has a radius of 187 pm and a Van der Waals radius of 240 pm. Lanthanum was first discovered by Carl Mosander in 1838. In its elemental form, lanthanum has a silvery white appearance.Elemental Lanthanum It is a soft, malleable, and ductile metal that oxidizes easily in air. Lanthanum is the first element in the rare earth or lanthanide series. It is the model for all the other trivalent rare earths and it is the second most abundant of the rare earths after cerium. Lanthanum is found in minerals such as monazite and bastnasite. The name lanthanum originates from the Greek word Lanthaneia, which means 'to lie hidden'.

Related Forms & Applications