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Comparison of the Pharmacokinetics of Gadolinium-Based and Iron Oxide-Based Contrast Agents inside the Lymphatic Structure using Magnetic Resonance Lymphangiography

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Abstract

Purpose

Gadolinium (Gd)-based contrast agents are primarily used for contrast-enhanced magnetic resonance lymphangiography (MRL). However, overcoming venous contamination issues remains challenging. This study aims to assess the MRL efficacy of the newly developed iron-based contrast agent (INV-001) that is specially designed to mitigate venous contamination issues. The study further explores the optimal dosage, including both injection volume and concentration, required to achieve successful visualization of the popliteal lymph nodes and surrounding lymphatic vessels.

Procedures.

All animals utilized in this study were male Sprague–Dawley (SD) rats weighing between 250 and 300 g. The contrast agents prepared were injected intradermally in the fourth phalanx of both hind limbs using a 30-gauge syringe in SD rats. MRL was performed every 16 min on a coronal 3D time-of-flight sequence with saturation bands using a 9.4-T animal machine.

Results

Contrary to Gd-DOTA, which exhibited venous contamination in most animals irrespective of injection dosages and conditions, INV-001 showed no venous contamination. For Gd-DOTA, the popliteal lymph nodes and lymphatic vessels reached peak enhancement 16 min after injection from the injection site and then rapidly washed out. However, with INV-001, they reached peak enhancement between 16 and 32 min after injection, with prolonged visualization of the popliteal lymph node and lymphatic vessels. INV-001 at 0.45 μmol (15 mM, 30 μL) and 0.75 μmol (15 mM, 50 μL) achieved high scores for qualitative image analysis, providing good visualization of the popliteal lymph nodes and lymphatic vessels without issues of venous contamination, interstitial space enhancement, or lymph node enlargement.

Conclusion

In MRL, INV-001, a novel T1 contrast agent based on iron, enables prolonged enhancement of popliteal lymph nodes and lymphatic vessels without venous contamination.

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Acknowledgements

We thank the core facilities of the Magnetic Resonance Core and the Comparative Pathology Core at the ConveRgence mEDIcine research cenTer (CREDIT), Asan Medical Center, for enabling the use of their equipment, services, and expertise.

Funding

This research was supported by the Bio&Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No. 2022M3A9G1014476); the National Research Foundation of Korea (NRF) (Grant No. 2019R1C1C1010887/ 2022R1Z1A1A01066589) funded by the Korean government (MIST); the R&D project linked to Biohealth Investment Infrastructure (Grant No. HI21C1317) funded by the Ministry of Health & Welfare/Biohealth Innovation Start-up Center, Republic of Korea; and Asan Institute of Life Sciences, Asan Medical Center, Republic of Korea (2021IL0030).

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Author notes

  1. Jeong Kon Kim, Yoonseok Choi and Dong-Cheol Woo contributed equally to this work.

Authors and Affiliations

  1. Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

    Yeon Ji Chae & Dong-Cheol Woo

  2. Convergence Medicine Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea

    Yeon Ji Chae, Chul-Woong Woo, Sang-Tae Kim & Dong-Cheol Woo

  3. Department of Radiology and Research Institute of Radiology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea

    Kyung Won Kim, Do-Wan Lee & Jeong Kon Kim

  4. Biomedical Research Center, Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea

    Kyung Won Kim

  5. Trial Informatics Inc, Seoul, Republic of Korea

    Kyung Won Kim & Mi-hyun Kim

  6. Inventera Inc, Seoul, Republic of Korea

    Ji-wook Kim & Tae-Hyun Shin

  7. Medical Research Institute, University of Ulsan College of Medicine, Gangneung Asan Hospital, Gangneung, Gangwondo, Republic of Korea

    Yoonseok Choi

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Correspondence to Jeong Kon Kim, Yoonseok Choi or Dong-Cheol Woo.

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Disclosure of Conflicts of Interest

K.W.K. & M.H.K. are employed by Trial Informatics. J.W.K. & T.H.S. are employed by Inventera Inc., a startup focused on developing nanoimaging agents. There are no other financial interests or potential conflicts of interest.

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Chae, Y.J., Kim, K.W., Kim, Mh. et al. Comparison of the Pharmacokinetics of Gadolinium-Based and Iron Oxide-Based Contrast Agents inside the Lymphatic Structure using Magnetic Resonance Lymphangiography. Mol Imaging Biol (2024). https://doi.org/10.1007/s11307-024-01918-w

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