Betanin-Based Contrast Agents for MRI: A Preliminary Experimental Study

Gadolinium-based contrast agents (GBCAs) are used in MRI, yet concerns about gadolinium ion release, tissue retention, rare adverse events, and environmental persistence have encouraged the search for alternatives. Prior work on plant-based extracts has been largely confined to gastrointestinal luminal imaging, with limited exploration in extraluminal organs as contrast agents.

To preclinically investigate the potentials of Betanin and beetroot-derived Betanin-based contrast agents (BBCA) in vitro and in vivo via oral, intravenous, and intraperitoneal administration, and to compare them with gadobutrol (a GBCA).

Prospective preclinical experimental study.

In vitro studies on human and mouse fibroblast cell lines, and in vivo tests involving male Wistar albino rats (n = 15) and male New Zealand albino rabbits (n = 2).

3 T, spin echo, and gradient echo sequences.

Betanin and BBCA compositions were characterized by mass spectrometry. Safety was assessed by in silico modeling, cytotoxicity, flow cytometry, histology, and blood biochemistry tests. Images of phantom solutions were used to characterize the paramagnetic features via MR relaxation times and relaxivities. In vivo contrast behavior in organs was evaluated following oral, intraperitoneal, and intravenous administrations.

The quantitative data were analyzed with Microsoft Excel and GraphPad Prism 9.0; p value < 0.05 was significant.

Betanin had greater molecular binding efficiency and therapeutic capacity. BBCA was less cytotoxic than gadobutrol. Some elements in BBCA were present in larger amounts than Betanin. T ₁ and T ₂ decreased with an increase in BBCA concentration, and r ₁ and r ₂ were estimated as 0.0014 and 0.0224 mmol^-1 s^-1, respectively. Both agents demonstrated contrast enhancements not only in the gastrointestinal lumen but also in the parenchymal organ, as well as in the vascular structure, with lower toxicity and antioxidative benefits. In particular, the enhancement in the liver was noteworthy.

Betanin and BBCA may be considered as viable options for contrast-enhanced abdominal MRI.