**4.1 Retention of gadolinium**

*Rare Earth Elements and Their Minerals*

*3.2.1 Key points of risk patients*

by a single eGFR value.

ing Gd-CM.

requiring dialysis [30].

particularly carefully.

*3.3.1 General points*

children aged under 1 year to protect the fetus.

contrast media administration for all patients.

**3.3 Use of gadolinium-based contrast agents**

GBCA in patients with GFR <30 mL/min/1.73 m2

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

adequate diagnostic examination.

iodinated contrast media.

• Never use more than 0.3 mmol/kg of any Gd-CM.

1.Approximately 40–50% of MRI patients receive Gd-CM.

No cases of NSF have been reported in patients with GFR greater than 60 ml/ min. The role of various possible cofactors in the pathogenesis of NSF is not proven. Pregnant patients. In the absence of specific information, it seems wise to manage pregnant patients, regardless of their renal function, in the same way as

In the use of GBCAs, serum creatinine should be measured before gadolinium

2.The percentage of patients with CKD 3, 4, and 5 varies in different institutions.

3.Serum creatinine and estimated GFR (eGFR) are not always very accurate indicators of true GFR. In particular, acute renal failure may not be indicated

4.Measurement of serum creatinine/eGFR before Gd-CM is mandatory before Gd-CM which have been associated with subsequent development of NSF.

5.Measurement of serum creatinine/eGFR is not necessary in all patients receiv-

Three GBCAs (gadodiamide, gadoversetamide, and gadopentetic acid) are currently FDA-contraindicated in patients with GFR <30 mL/min/1.73 m2

American College of Radiology (ACR) recommends screening GFR of any patients with known or suspected renal impairment and advises against the use of any

1.The risk of inducing NSF must always be weighed against the risk of denying patients gadolinium-enhanced scans which are essential for patient management.

• Always use the smallest possible amount of the contrast agent to achieve an

• Never use gadolinium as a contrast agent for radiography, computed tomography, or angiography as a method of avoiding nephropathy associated with

2.In patients with impaired renal function, liver transplant patients, and neonates, the benefits and risks of gadolinium enhancement should be considered

. The

, suffering acute kidney injury, or

**56**

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

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

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

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

gadolinium behind in bone than did ProHance (Gd-HP-DO3A). These results would indicate two important issues: (1) chelate stability and (2) affinity of GBCA to the bone. Linear GBCAs like Omniscan (Gd-DTPA-BMA) would release more Gd3+ ions than macrocyclic GBCAs like ProHance (Gd-HP-DO3A). Since the bone is a known natural repository for unchelated Gd3+ ions, free Gd3+ ions released from Omniscan (Gd-DTPA-BMA) would retain bone. Another reason to deposit gadolinium to bone would be the affinity of GBCAs to bone. Hydroxyapatite structure is similar to the structure of DTPA. It might be one of causes for linear GBCAs, especially Gd-DTPA or Gd-DTPA-BMA to retain bone.
