3.In patients with CKD 4 and 5 (<30 ml/min):


**57**

*Current Clinical Issues: Deposition of Gadolinium Chelates*

**4. Gadolinium deposition in human body**

important than injection doses [27, 37–39].

to reveal the distribution of gadolinium in vivo [41, 42].

**4.1 Retention of gadolinium**

**3.4 How to choose gadolinium-based contrast agents?**

There are differences in the incidence of NSF with different GBCAs, which appear to be related to differences in physicochemical properties and stability. Since macrocyclic GBCAs are preorganized rigid rings of almost optimal size to cage the gadolinium ions which have high stability compared with linear GBCAs, macrocyclic GBCAs are recommended to inject to patients with mild to moderate CKD. According to the current knowledge about the properties of the different agents and the incidence of NSF, macrocyclic GBCAs should be used for high-risk

The retention of gadolinium in the human body has become an issue of considerable global interest these days. Gadolinium retention was observed in the bone and in the brain in patients without renal failure [32]. The pharmacokinetics of different gadolinium chelates have been studied in healthy patients and in those with varying degrees of renal impairment. The main pathway of elimination is glomerular filtration [33]. The mean elimination half-life of GBCAs is 1.3–1.5 h. In patients with severe renal insufficiency, the half-life increases to 34.3 h [7]. Currently, it is known that gadolinium is retained in body tissues, regardless of levels of renal function or even GBCA stability [22]. Higher concentrations appear to occur in patients

Our recent study found that a long-term Gd retention for GBCAs was almost unaffected by renal function [35, 36]. This finding suggested that the chemical structures of retained Gd may not be homogeneous and some Gd could be slowly eliminated after being initially retained in the tissues. Moreover, Gd retention was greater when linear GBCA was administered, than macrocyclic GBCA. However, the presence of the blood–brain barrier (BBB) likely plays a role in the mechanism of Gd retention in the brain. The mechanism of retention and the shapes of GBCAs have not been adequately revealed yet. Although injection doses should be minimized for all patients, some reports suggest that injection times would be more

Gadolinium has some isotopes such as 154Gd, 155Gd, 156Gd, 157Gd, 158Gd, and 160Gd as stable isotopes and 152Gd as a radioisotope. Biodistribution study of various GBCAs was performed in 1995 using a radioisotope of 153Gd. 153Gd was labeled to gadopentetate (Magnevist), gadoteridol (ProHance), gadoterate (Dotarem), and gadodiamide (Omniscan) [40]. All GBCAs were excreted from animal body within 60 min, and GBCAs in blood pool were completely disappeared. The liver, kidney, femur bone, and gastrointestinal tract still retain GBCAs until 14 days. These days the measurements of gadolinium are performed by inductively coupled plasma mass spectroscopy (ICP-MS). In our researches, either 158Gd or 160Gd is measured by ICP-MS. The technology of imaging mass would contribute

Gregory WW reported the gadolinium concentration remaining in human bone tissue after administration of 0.1 mmol/kg of two types of GBCA, Omniscan (Gd-DTPA-BMA) or ProHance (Gd-HP-DO3A), to patients undergoing hip replacement surgery. Tissue retention in bone for Omniscan (Gd-DTPA-BMA) was significantly higher than those for ProHance (Gd-HP-DO3A) measured by ICP-MS. Omniscan (Gd-DTPA-BMA) left approximately four times more

with renal impairment or after exposure to less stable GBCAs [34].

*DOI: http://dx.doi.org/10.5772/intechopen.91260*

patients [31].

## **3.4 How to choose gadolinium-based contrast agents?**

There are differences in the incidence of NSF with different GBCAs, which appear to be related to differences in physicochemical properties and stability. Since macrocyclic GBCAs are preorganized rigid rings of almost optimal size to cage the gadolinium ions which have high stability compared with linear GBCAs, macrocyclic GBCAs are recommended to inject to patients with mild to moderate CKD. According to the current knowledge about the properties of the different agents and the incidence of NSF, macrocyclic GBCAs should be used for high-risk patients [31].
