Quantitative MRI Pharmacokinetic Modeling and MALDI Mass Spectrometry Imaging Biodistribution of a pH Mapping MRI Contrast Agent.

Preclinical animal study involving synthesis, biodistribution, pharmacokinetics, and MRI imaging in mice

“This study was designed as an exploratory feasibility assessment, and no formal a priori power calculation was performed.”

Male C57BL/6J mice

“Male C57BL/6J mice (3-4 months old) were anesthetized with 1.5-2.0% isoflurane in oxygen and placed on a heated imaging cradle to maintain body temperature at 37 °C.”

Dynamic MRI acquisition of approximately 30 minutes post-injection, with histological assessment at 48 hours

“A total of 180 time points were captured over ~30 mins.”

MALDI-MSI confirmed selective renal localization of the probe with negligible accumulation in liver or pancreas, and the probe was excreted intact in urine.

“MALDI-MSI confirmed selective renal localization and unmetabolized probe in urine, with negligible liver or pancreas accumulation.”

Voxel-wise pH maps reproduced the expected corticomedullary gradient with mean pH values of 6.86 in the cortex, 6.80 in the outer medulla, and 6.61 in the inner medulla.

“Voxel-wise pH maps reproduced the expected corticomedullary gradient (mean ± SD): cortex 6.86 ± 0.087, outer medulla 6.80 ± 0.073, inner medulla 6.61 ± 0.079, with pH estimates largely dose-independent.”

No formal a priori power calculation was performed, and invasive in vivo pH validation using microelectrodes was not conducted in the same animals.

“We did not perform invasive in vivo pH validation (e.g., microelectrode) in the same animals.”