OXIDOREDUCTIVE STATE - THE MAJOR DETERMINANT FOR CELLULAR RETENTION OF TECHNETIUM-99M-HMPAO

Several clinical observations have suggested that HMPAO cerebral uptak e might be related not only to regional cerebral perfusion but also to the nature of the lesion. Our aim was to investigate at the cellular level the nature of the process(es) involved in HMPAO accumulation in vitro. Methods: Time-course incorporation of HMPAO was studied in a fa st-growing human premonocytic line, U937, in a human astrocytic-derive d cell line, U373 and a human hybridized endothelial cell line, EaHy92 6. Minimal differences of HMPAO retention between these cell lines wer e observed and plateau of %U-HMPAO (cpm cells/cpm standard of injected ) were achieved within 2 hr. Because HMPAO cell retention was related to the intracellular content in glutathione, experiments studying effe cts of redox were conducted by preexposing U937 cells to D,L-buthionin e-sulfoximine (BSO), N-acetyl-L-cystein (NAG), D,L dithiothreitol or 2 -Mercaptoethanol. Results: Overnight incubation with NAC or BSO did no t significantly modified the kinetic of Tc-99m-HMPAO incorporation whi le overnight incubation with NAC resulted in a 2-fold increase in intr acellular gluthatione content and overnight incubation with BSO nearly abolished the intracellular glutathione content. At the opposite, pre sence of these reducing agents in the medium during the experiments co mpletely abolished Tc-99m-HMPAO retention. Conclusion: Our data thus p rovide in vitro evidence to support that overall intracellular retenti on of HMPAO is more dependent upon the redox activity of the tissue th an the intracellular glutathione content. SPECT-HMPAO may accurately r eflect regional cerebral blood flow in a normal stale but possibly not in all pathological situations in which cell metabolism disturbances are charac terized by alterations in the redox status.