Comparative evaluation of the magnetic resonance contrast properties of gadolinium-based contrast agents

Background. Restrictions on the use of gadolinium-containing radiocontrast agents due to the risk of acute and long-term complications drive the search for new, safer, and more effective gadolinium-based nanoparticle formulations.

Aim. Comparative assessment of the magnetocontrast properties of a gadolinium nanocomposite and a gadolinium-based contrast agent.

Methods. The dynamics of organ accumulation and visual MRI patterns were studied in 5 healthy female Wistar rats using a Siemens Avanto device with a magnetic field of 1.5 T. Anesthetized animals were placed in a ventral position within the head coil, after which a preliminary MRI scan was performed. A gadolinium nanocomposite solution and a reference agent (Omniscan®) were injected at equivalent gadolinium doses into the lateral tail vein or into the abdominal cavity, followed by repeat MRI scans with image acquisition every 2–3 minutes. The primary imaging areas were the abdominal cavity and retroperitoneal space, including the thoracic cavity.

Results. Comparative analysis showed that gadolinium nanoparticles stabilized with arabinogalactan exhibit magnetocontrast properties, as evidenced by T1-weighted image enhancement of the liver parenchyma after intravenous administration and of the abdominal cavity after intraperitoneal administration. The magnetocontrast image of the kidneys and bladder was higher after Omniscan® administration than after gadolinium nanocomposite administration. However, the maximum contrast coefficient of the gadolinium nanocomposite in the liver parenchyma increased by 20 % compared to baseline. Omniscan® administration resulted in a 13 % increase in T1-weighted image intensity of the liver parenchyma.

1. Rudnick MR, Wahba IM, Leonberg-Yoo AK, Miskulin D, Litt HI. Risks and Options with Gadolinium-Based Contrast Agents in Patients with CKD: A Review. Am J Kidney Dis. 2021; 77(4): 517–528. doi: 10.1053/j.ajkd.2020.07.012

2. Parillo M, Mallio CA, Van der Molen AJ, Rovira À, Ramalho J, Ramalho M, et al. Skin Toxicity After Exposure to Gadolinium-Based Contrast Agents in Normal Renal Function, Using Clinical Approved Doses: Current Status of Preclinical and Clinical Studies. Invest Radiol. 2023; 58(8): 530–538. doi: 10.1097/RLI.0000000000000973

3. Ramalho J, Ramalho M. Gadolinium Deposition and Chronic Toxicity. Magn Reson Imaging Clin N Am. 2017; 25(4): 765–778. doi: 10.1016/j.mric.2017.06.007

4. Layne Kerry A, Dargan Paul I, Archer John RH, Wood David M. Gadolinium deposition and the potential for toxicological sequelae – A literature review of issues surrounding gadolinium-based contrast agents. Br. J. Clin. Pharmacol. 2018; 84(11): 2522–2534. doi: 10.1111/bcp.13718

5. Chauhan G, Upadhyay A. Gadolinium-based contrast agent-induced neurotoxicity: seeing is believing! BMJ Case Rep. 2021; 14(1): e241372. doi: 10.1136/bcr-2020241372

6. Sieber Martin A, Lengsfeld Ph, Frenzel T, Golfier S, Schmitt-Willich H, Siegmund F, et al. Preclinical investigation to compare different gadolinium-based contrast agents regarding their propensity to release gadolinium in vivo and to trigger nephrogenic systemic fibrosis-like lesions. Eur Radiol. 2008; 18(10): 2164-73. doi: 10.1007/s00330-008-0977-y

7. Rogosnitzky M, Branch S. Gadolinium-based contrast agent toxicity: a review of known and proposed mechanisms. Biometals. 2016; 29: 365–376. doi: 10.1007/s10534-016-9931-7

8. Mercantepe T, Tumkaya L, Celiker FB, Topal SZ, Cinar S, Akyildiz K, et al. Effects of gadolinium-based MRI contrast agents on liver tissue. J. Magn. Reson. Imaging. 2018; 48: 1367–1374. doi: 10.1002/jmri.26031

9. Coimbra S, Rocha S, Sousa NReis, Catarino C, Belo L, Bronze-da-Rocha E, et al. Toxicity Mechanisms of Gadolinium and Gadolinium-Based Contrast Agents-A Review. Int. J. Mol. Sci. 2024; 25(7): 4071. doi: 10.3390/ijms25074071

10. Kotb S, Detappe A, Lux F, Appaix F, Barbier EL, Tran VL, et al. Gadolinium-Based Nanoparticles and Radiation Therapy for Multiple Brain Melanoma Metastases: Proof of Concept before Phase I Trial. Theranostics. 2016; 6(3): 418-27. doi: 10.7150/thno.14018

11. Maury P, Texier M, Genestie C, Morice P, Bockel S, Gouy S, et al. Theragnostic Gadolinium-Based Nanoparticles Safely Augment X-ray Radiation Effects in Patients with Cervical Cancer. ACS Nano. 2024; 18(26): 16516-16529. doi: 10.1021/acsnano.3c12537

12. Sukhov BG, Konkova TV, Ivanov AV. Water-soluble magnetoactive nanobiocomposites of gadolinium flavonoid complexes based on a natural conjugate of arabinogalactan with bioflavonoids and a method for obtaining these nanobiocomposites. Patent RF № 2706705. – 2019. Publ. 20.11.2019 (In Russ.).

13. Trofimov BA, Sukhov BG, Aleksandrova GP, Medvedeva SA, Grishchenko LA, Mal’kina AG, et al. Arabinogalactan-based nanocomposites with magnetic, optical, catalytic and biologically active properties. Doklady Akademii Nauk. 2003; 393(5): 634-635.

14. Куценко С.А. Основы токсикологии. М.: Фолиант; 2004. [Kutsenko SA. Fundamentals of Toxicology. M.: Foliant; 2004. (In Russ.).

15. Gomzikova MO, Malanyeva AG, Siraeva ZYu. Fundamentals of biomedical research on laboratory animals: textbook. Kazan: PH “Meddock”; 2021. (In Russ.).

16. Kaneo Y, Ueno T, Tanaka T, Jwase H, Yamaguchi Y, Uemura T. Pharmacokinetics and biodisposition of fluorescein-labeled arabinogalactan in rats. Jnt. J. Pharm. 2000; 201(1): 59–69. doi: 10.1016/s0378-5173(00)00405-1

17. Davies J, Siebenhandl-Wolff P, Tranquart F, Jones P, Evans P. Gadolinium: pharmacokinetics and toxicity in humans and laboratory animals following contrast agent administration. Arch Toxicol. 2022; 96(2): 403–429. doi: 10.1007/s00204-021-03189-8