Departments of Radiology and Research Institute of Radiology, Asan Medical Center, College of Medicine, University of Ulsan, Olymphic-ro 43 Gil 88, Songpa-gu, Seoul, 138-735, Republic of Korea.
Departments of Medical Science, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Sci Rep. 2024 May 7;14(1):10502. doi: 10.1038/s41598-024-61104-4.
We aimed to conduct a proof-of-concept study of INV-001 in visualizing lymphatic vessels and nodes without venous contamination and to determine the optimal dose condition of INV-001 for magnetic resonance lymphangiography (MRL) in healthy beagles. MRL was performed using a 3.0-Tesla (T) whole body clinical magnetic resonance imaging (MRI) scanner. A dose-finding study of INV-001 for MRL in beagles (N = 6) was carried out according to an adaptive optimal dose finding design. For the reproducibility study (N = 6), MRL was conducted at selected INV-001 doses (0.056 and 0.112 mg Fe/kg) with a 15 mM concentration. Additionally, an excretion study (N = 3) of INV-001 was conducted by analyzing T, T, and T* maps of the liver and kidney 48 h post-administration. INV-001 administration at doses of 0.056 and 0.112 mg Fe/kg (concentration: 15 mM) consistently demonstrated the visualization of contrast-enhanced lymphatic vessels and nodes without venous contamination in the beagles. The contrast enhancement effect was highest at 30 min after INV-001 administration, then gradually decreasing. No toxicity-related issues were identified during the study. After 48 h, the T, T, and T* values in the liver and both kidneys were found to be comparable to the pre-administration values, indicating thorough INV-001 excretion. The optimal dosing conditions of INV-001 for MRL for contrast-enhanced visualization of lymphatic vessels and nodes exclusively with no venous contamination in beagles was determined to be 0.056 mg Fe/kg with a 15 mM concentration.
我们旨在进行一项 INV-001 用于可视化淋巴管和淋巴结而不伴有静脉污染的概念验证研究，并确定 INV-001 用于健康比格犬磁共振淋巴造影术（MRL）的最佳剂量条件。MRL 使用 3.0-Tesla（T）全身临床磁共振成像（MRI）扫描仪进行。根据适应性最佳剂量发现设计，对 INV-001 用于比格犬 MRL 的剂量发现研究（N=6）进行了研究。为了进行重复性研究（N=6），在选定的 INV-001 剂量（0.056 和 0.112mg Fe/kg）下进行 MRL，浓度为 15mM。此外，通过分析肝和肾的 T、T 和 T图谱，在给药后 48 小时进行 INV-001 的排泄研究（N=3）。在比格犬中，以 0.056 和 0.112mg Fe/kg（浓度：15mM）的剂量给药 INV-001 可一致显示无静脉污染的对比增强淋巴管和淋巴结。在 INV-001 给药后 30 分钟，造影增强效果最高，然后逐渐下降。在研究期间未发现与毒性相关的问题。给药后 48 小时，肝和双肾的 T、T 和 T值与给药前的值相当，表明 INV-001 已完全排泄。确定 INV-001 用于 MRL 的最佳剂量条件为 0.056mg Fe/kg，浓度为 15mM，用于比格犬的淋巴管和淋巴结的对比度增强可视化，仅无静脉污染。
