Deuterated α-Aminoisobutyric Acid (AIBA-d6) as a Novel Contrast Agent for Deuterium Magnetic Resonance Spectroscopy (DMRS)

Introduction: Deuterium magnetic resonance spectroscopy (DMRS) is a promising approach for
the non-invasive investigation of pathological conditions. Organic compounds with hydrogen
atoms replaced by deuterium can serve as contrast agents for DMRS. Choosing the right contrast
agent allows for obtaining spectra on 3T scanners and evaluating malignant tumors. In the study, we
investigated α-aminoisobutyric acid with all six carbon-bound hydrogen atoms replaced with
deuterium (AIBA-d6).
Methods: The biodistribution of AIBA-d6 was studied after a single intravenous administration
in Wistar rats at a dose of 125 mg/kg. Concentrations were measured in plasma, 17 organs and
tissues, urine, and feces from 5 minutes to 48 hours. Acute tolerability was assessed after a single
high dose (2000 mg/kg). Tumor visualization was confirmed using 2-h DMRS in rodents with
4T1 breast carcinoma or C6 glioma. AIBA-d6's ability to detect human glioblastomas was tested
using phantom models and a 3T scanner.
Results: Acute toxicity study showed no pathological changes within 7 days after a single
intravenous administration at the maximum tested dose of 2000 mg/kg. AIBA-d6 reached its
maximum plasma concentration (C_max 297.3 ± 131.7 μg/mL) immediately after intravenous
administration and then declined biphasically to 12.3 ± 4.2 μg/mL at 48 h. AIBA-d6 was not
metabolized; the highest concentration was observed in the kidneys (C_max 1028 ± 139 μg/g;
T_max ≈ 1 h), indicating renal clearance. Urinary concentrations were high during the 0–6 h
interval (2203 ± 1131 μg/mL), whereas fecal excretion was minimal. Accumulation in tumors
was confirmed by DMRS on a Bruker 7T scanner. This accumulation was associated with
overexpression of A/SNAT1-2 transporters. Phantom studies showed that tumor levels were high
enough for detection in human brain tumors using a clinical 3T scanner within 17–30 minutes.
Conclusions: AIBA-d6 is a promising contrast agent for the visualization and detection of
malignant brain tumors by DMRS.