Brain tumor enhancement in magnetic resonance imaging: dependency on the level of protein binding of applied contrast agents

Abstract

Purpose: To evaluate the dependency of tumor contrast enhancement (CE) in regard to protein-binding properties of contrast agents, using 4 different agents with a wide range of protein-binding capacities in a standardized rat brain glioma model.

Material and methods: Sixteen rats with implanted brain gliomas were evaluated at 1.5 T with a multielement wrist coil in 2 different comparative settings. In both groups, a non-protein-binding agent (gadopentetate dimeglumine, Bayer Healthcare Inc.) and a weak protein-binding agent (gadobenate dimeglumine, Bracco Diagnostics Inc.) were applied and compared with either a approximately 90% protein-binding agent (group A; B22956/1, Bracco Research USA) or a approximately 50% protein-binding agent (group B; BRU 52, Bracco Research USA). All agents were applied at a dose of 0.1 mmol/kg and a single data acquisition with standard T1-weighted turbo spin-echo sequence (TR/TE = 480/15 ms) was initiated 10 seconds after injection. Evaluation of tumor CE and contrast-to-noise ratio (CNR) was based on region of interest measurements within the tumor and remote normal brain.

Results: With B22956/1 (group A), CE increased by 93% in comparison with gadobenate dimeglumine (15.0 +/- 5.3 vs. 7.8 +/- 2.7; P = 0.010) and by 136% in comparison with gadopentetate dimeglumine (15.0 +/- 5.3 vs. 6.4 +/- 1.9; P = 0.013). CNR using B22956/1 increased by 116% in comparison with gadobenate dimeglumine (14.0 +/- 5.9 vs. 6.5 +/- 2.6; P = 0.015) and increased by 138% in comparison with gadopentetate dimeglumine (14.0 +/- 5.9 vs. 5.9 +/- 1.7; P = 0.034). Using BRU 52 (group B), CE increased by 60% in comparison with gadobenate dimeglumine (21.7 +/- 1.4 vs. 13.6 +/- 2.5; P = 0.013) and by 94% in comparison with gadopentetate dimeglumine (21.7 +/- 1.4 vs. 11.2 +/- 0.5; P < 0.0001). CNR using BRU 52 increased by 72% in comparison with gadobenate dimeglumine (21.2 +/- 1.3 vs. 12.3 +/- 3.1; P = 0.0002) and by 122% in comparison with gadopentetate dimeglumine (21.3 +/- 1.3 vs. 9.6 +/- 0.8; P < 0.0001).

Conclusion: The protein-binding capacity of gadolinium chelates shows a significant impact on CE and CNR in brain tumors with disrupted blood-brain barrier. In comparison with currently approved agents, high albumin-binding agents show further improved brain tumor CE. However, the time course of enhancement and optimal time frame for scanning after injection of agents with higher protein-binding capacities (approximately 50%-90%) has yet to be evaluated.