Gadoquatrane in Contrast-enhanced Head-and-neck and Liver Magnetic Resonance Imaging: A Preclinical Dose-Response Study in Pigs.

Abstract

Objectives: The objective of the study was to investigate the dose-response (signal enhancement) relationship and signal-enhancement kinetics of gadoquatrane in different anatomic regions employing different MRI pulse sequences. Gadoquatrane is a novel high-relaxivity, extracellular macrocyclic gadolinium-based contrast agent with tetrameric structure that has the potential to be used at lower Gd doses than long-established contrast agents.

Materials and methods: In this exploratory, prospective crossover study, 7 healthy pigs underwent contrast-enhanced MRI examinations with gadoquatrane (0.01, 0.03, and 0.06 mmol Gd/kg body weight) and standard doses (0.1 mmol Gd/kg) of 2 comparators, gadobutrol and gadoterate meglumine. MRI was performed on a 1.5T scanner under conditions typically used in clinical routine. Immediately after contrast-agent injection, multiphase liver MRI was done (VIBE sequence). Steady-state head-and-neck MRI followed (spin-echo and FLASH sequences alternating from 2 to 32 min after injection). Image evaluation was based on changes in signal intensity from baseline [relative signal enhancement (RSE)]. Simple linear regression analysis was used to investigate the relationship between RSE and gadoquatrane dose. The regression equations were used to estimate the comparator-equivalent doses of gadoquatrane.

Results: The RSE achieved with gadoquatrane in steady-state head-and-neck MRI and multiphase liver MRI increased with dose in all anatomic structures examined, independent of the contrast-agent distribution phase and the pulse sequence employed. Linear regression analysis showed that generally a linear model fitted the dose-response data well ( r2 ≥ 0.84). However, in spin-echo images of the cavernous sinus and VIBE images of the hepatic vein, the areas with the strongest RSE, a disproportionately low RSE was seen with the highest gadoquatrane dose ( r2 of 0.78 and 0.48, respectively).RSE equivalent to the RSE achieved with gadoterate meglumine and gadobutrol at standard dose was achieved with gadoquatrane at doses between 0.031 to 0.039 mmol Gd/kg and 0.040 to 0.049 mmol Gd/kg, respectively. Largely parallel RSE-versus-time curves suggest similar signal-enhancement kinetics for gadoquatrane and the comparators.

Conclusions: The study suggests that gadoquatrane, which demonstrated signal-enhancement kinetics similar to those of gadobutrol and gadoterate meglumine, might be utilized effectively at a dose below 0.05 mmol Gd/kg body weight, independent of the anatomic structure investigated and the pulse sequence employed. Overall, the study supports and complements the results of the clinical dose-response study of gadoquatrane.