Potential of N-acetylated-para-aminosalicylic acid to accelerate manganese enhancement decline for long-term MEMRI in rodent brain

Manganese (Mn²⁺)-enhanced MRI (MEMRI) is a valuable imaging tool to study brain structure and function in normal and diseased small animals. The brain retention of Mn²⁺ is relatively long with a half-life (t_1/2) of 51-74 days causing a slow decline of MRI signal enhancement following Mn²⁺ administration. Such slow decline limits using repeated MEMRI to follow the central nervous system longitudinally in weeks or months. This is because residual Mn²⁺ from preceding administrations can confound the interpretation of imaging results. We investigated whether the Mn²⁺ enhancement decline could be accelerated thus enabling repeated MEMRI, and as a consequence broadens the utility of MEMRI tests. New methodsWe investigated whether N-acetyl-para-aminosalicylic acid (AcPAS), a chelator of Mn²⁺, could affect the decline of Mn²⁺ induced MRI enhancement in brain. Results and conclusionTwo-week treatment with AcPAS (200mg/kg/dose×3 daily) accelerated the decline of Mn²⁺ induced enhancement in MRI. In the whole brain on average the enhancement declined from 100% to 17% in AcPAS treated mice, while in PBS controls the decline is from 100% to 27%. We posit that AcPAS could enhance MEMRI utility for evaluating brain biology in small animals. Comparison with existing methodsTo the best of our knowledge, no method exists to accelerate the decline of the Mn²⁺ induced MRI enhancement for repeated MEMRI tests.