High resolution AMS imaging of radiocarbon in biomedical applications

Abstract

Radiocarbon has been an important labelling element in biological metabolism studies. By interfacing an accelerator mass spectrometer (AMS) with a scanning microprobe secondary ion source, we have imaged the uptake of radiocarbon labelled metabolic or neurotransmitter amino acids by neurons and glial cells of rats and gerbils at high resolution (1 micron), high sensitivity and in a short time. The biological samples are prepared and sectioned serially at 0.5 μm thickness using standard histological procedures. The adjacent sections to those used for AMS imaging were either immunolabelled with antibodies to GABA to reveal GABA-containing cells, or stained with toluidine blue to visualise every cell. Therefore, the distribution of radiocarbon revealed by AMS could be matched to that of the cells. By simultaneously measuring the 14C, 13C and 12C signals, we can demonstrate that the localised peaks of radiocarbon could be readily identified and matched to GABA-immunopositive neurons and glial cells by aligning the radiocarbon deficient blood vessels with the vessels in the adjacent histologically stained section. The results revealed the selective uptake of the neurotransmitter, GABA and that of metabolic amino acid, leucine. The technique compares favourably with high resolution autoradiography and provides great potential for improving the analysis of molecular interactions in and between cells.