Research Into MRI Contrast Agent Wins Neuroradiology Research Award
RSNA Kuo York Chynn Neuroradiology Research Award presented during RSNA 2024
An investigational MRI contrast agent provides comparable clinical efficacy to existing agents at up to a 60% lower dose of gadolinium, according to new research out of Germany. The work earned the 2024 Kuo York Chynn Neuroradiology Research Award for the top neuroradiology research paper presented during the RSNA annual meeting.
Gadolinium-based contrast agents (GBCAs) are widely used to improve the contrast of different tissues in the body on MR images via altering relaxation times of water protons in the body. Guidelines from health authorities and scientific bodies recommend using the lowest effective dose while maintaining diagnostic efficacy.
Gadoquatrane is an investigational macrocyclic contrast agent that has been under development in recent years. Its distinct tetrameric structure with high stability and high relaxivity has the potential to enable a lower clinical gadolinium dose in contrast-enhanced MRI for patients.
Petra Palkowitsch, MD, from Bayer AG in Berlin, who is leading the clinical development of gadoquatrane, and her colleagues have been studying gadoquatrane intensively in recent years.
“The purpose of our research was to identify a dose for the further clinical development of gadoquatrane,” she said. “For this, we conducted two clinical trials.”
Gadoquatrane Showed Linear Signal Boost at Lower Doses
The Phase 1 study focused on identifying a dose of gadoquatrane that would yield similar relative signal enhancement as gadobutrol, a commonly used macrocyclic GBCA, at 0.1 millimoles of
gadolinium per kilogram of bodyweight (mmol Gd/kg). Healthy participants received different doses of gadoquatrane, and the researchers looked at signal enhancement data in relation to dose and assessed five regions of the head and neck area representing different degrees of vascularization.
For all five regions, gadoquatrane demonstrated a linear increase in relative signal enhancement with dose. The equivalent dose was less than half the gadolinium dose of gadobutrol for each region.
Based on the results of the Phase 1study, the starting dose of 0.04 mmol Gd/kg was selected for the multicenter Phase 2 study. This represents a gadolinium dose reduction of 60% compared to the macrocyclic GBCAs dosed at 0.1 mmol Gd/kg body weight. The patients in the study underwent contrast-enhanced MRI for known or highly suspected central nervous system (CNS) lesions. Subjects received single intravenous injections of gadoquatrane with corresponding blinded review. The researchers used qualitative endpoints like image preference and lesion visualization parameters to assess different CNS lesions and pathologies.
The images were compared to images with gadobutrol and assessed in a blinded independent central read by three neuroradiologists.
“The study met its primary and secondary endpoints with the first tested dose,” Dr. Palkowitsch said. “The new investigational macrocyclic gadoquatrane is a promising GBCA in development for MRI and MR angiography at a substantially reduced gadolinium dose compared to macrocyclic GBCAs dosed at 0.1 mmol Gd/kg body weight.”
The Bayer research team used the dose identified in the two studies mentioned above for the Phase 3 studies evaluating the efficacy and safety of gadoquatrane. They looked at gadoquatrane in the imaging of CNS, other body regions and in pediatric patients. Gadoquatrane met the primary and main secondary efficacy endpoints of the studies assessing visualization parameters and lesion detection. Results in the pediatric group demonstrated that the pharmacokinetic behavior of gadoquatrane in children is similar to that in adults.
The observed safety profile in adults and pediatric patients from birth to age 17 years was consistent with previous data on gadoquatrane and other macrocyclic GBCAs. No new safety signals were observed. All studies are planned to be presented at future congresses. Bayer plans to submit a comprehensive data package which will include the study results to health authorities worldwide to secure marketing authorization for gadoquatrane.
Funded with a donation by internationally renowned neuroradiologist and longtime RSNA member Kuo York Chynn, MD, the RSNA Kuo York Chynn Neuroradiology Research Award provides $3,000 to the author of the top neuroradiology research paper presented at the RSNA annual meeting.
Dr. Palkowitsch credited her colleagues at Bayer for their dedicated work on gadoquatrane research over the years, together with the work of investigators and study sites worldwide. “Receiving this award is certainly one of the highlights of my career and I am grateful to the donor of the award as well as the peers who selected our work,” she said. “This award is also a great motivator for the entire team to continue working to make our investigational MR contrast agent available for patients and their treating physicians.”
For More Information
Learn more about the Kuo York Chynn Neuroradiology Research Award.
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