Urinary ImagingE2371. Gadolinium Deposition in Tissue After Long-Term Intraperitoneal GBCA Injection in Rats
Langer R, Neidl v Gorkom K, Mohamed N. College of Medicine and Health , Al Ain, United Arab Emirates
Address correspondence to R. Langer (email@example.com)
Objective: No published data of gadolinium deposition in cutis and subcutis or in other organs are available after long-term intraperitoneal (IP) injection of gadolinium-based contrast agents (GBCA) in rats. For animal experiments in rats, IP injection is a practical and established technique for drug testing. In theory, slower absorption, compared with an IV regimen, may cause prolonged exposure to the administered compounds, in our study GBCA; and therefore may probably lead to higher tissue deposits of gadolinium.
Materials and Methods: The study was approved by our institutional animal ethics review board (A8/07). IP injections of six different GBCA were given in Wistar rats for four consecutive weeks at doses of 2.5 mmol/kg BW. Two groups received GBCA at doses of 5.0 mmol/kg body weight, and one control group was treated with IP saline injections (five rats/group). One week after cessation of IP GBCA injections, all rats were sacrificed, and multiple specimens were secured. Gadolinium deposition in cutis, subcutis, and kidneys was assessed by inductively coupled plasma atomic emission spectrometry.
Results: In total 45 rats in nine groups with five animals each were examined according to the described protocol. The applied GBCA doses in our animal experiments (IP injection of 2.5 mmol/kg body weight and 5 mmol/kg body weight) are consistent with elsewhere published experimental data. Gadolinium deposits in cutis and subcutis after IP GBCA injections were three to five times higher than after IV injection of 2.5 mmol/kg body weight, and considerably higher at doses of 5.0 mmol/kg body weight. The maximum gadolinium accumulation in cutis and subcutis was 94.2 mg/kg after doses of 2.5 mmol/kg body weight gadodiamide, and 695.8 mg/ kg after 5.0 mmol/kg body weight gadodiamide, respectively. Gadolinium accumulation in renal tissue was even three times higher than in cutis and subcutis. Gadodiamide (Omniscan) showed the highest gadolinium deposition followed by gadoversetamide (Optimark), and gadopentetate dimeglumine (Magnevist), similar to patients with nephrogenic systemic fibrosis (NSF). In our animal experiments the rats did not show clinical or histologic findings of NSF.
Conclusion: High gadolinium deposition in tissue could be confirmed after long-term IP GBCA injection. Our results show noticeably greater gadolinium accumulation in cutis, subcutis, and kidneys than in published data with IV GBCA application at equal doses. The highest gadolinium tissue concentration in the skin was observed after IP administration of gadodiamide, gadoversetamide, and gadopentetate dimeglumine. In addition to the total amount of gadolinium deposit in tissue, different parameters of IV GBCA application, such as peak and frequency of injection, seem to be important for NSF development in the animal model.