Cellular basis of ECD brain retention.
Clinical observations have shown discrepancies between ECD and HMPAO regional cerebral perfusion, particularly in brain tumors and during stroke recovery. We investigated the nature of the process(es) involved in ECD accumulation in vitro at the cellular level.


METHODS
Time course incorporation of ECD was studied in a fast-growing human premonocytic line, U937, in a human astrocytic-derived cell line, U373, and a human hybridized endothelial cell line, EaHy926. Cells were further used in experiments aiming to correlate esterase activity and ECD retention.


RESULTS
Significant differences in ECD retention between these cell lines were observed: %UECD (cpm cells/cpm standard of injected) plateaued within 2 hr in all cases but %UECD was significantly higher in U937 cells (25.1 +/- 3.9% at 120 min) than in the other cell lines (6.1 +/- 0.7% and 8.2 +/- 2.0% at 120 min for U373 and EaHy926, respectively). Contrary to what we expected, total cellular esterase activity (EATOT) was inversely correlated to %UECD.EATOT was 5-fold lower in U937 cells than in U373 and 20-fold lower than in EaHy926. Thus, we compared the membranar to the cytosolic esterase activity of U937 and analyzed the influence of temperature and diisopropylfluorophosphate (DFP, an inhibitor of cytosolic esterase activity) on both ECD retention and enzymatic activities. When cells were exposed to DFP, %UECD was reduced by 80%; while when cells were maintained at 4 degrees C, %UECD continuously increased, corresponding to a passive diffusion since both cytosolic and membranar esterase activities were inhibited.


CONCLUSIONS
For optimal uptake of ECD, the membranar fraction of the esterase activity has to be low, while, in contrast, the cytosolic fraction of the esterase activity plays an important role in ECD cell retention. ECD-SPECT is likely able to reflect regional cerebral blood flow in normal and pathological states accurately, but in the event of unusual observations, the membranar esterase activity should be considered to explain reduced ECD retention.
Jacquier-Sarlin
M R
MR
Department of Radiology, Geneva University Hospital, Switzerland.
Polla
B S
BS
Slosman
D O
DO
D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D003545:Cysteine / Q000031:analogs & derivatives*; D003600:Cytosol / Q000201:enzymology; D004950:Esterases / Q000378:metabolism; D006801:Humans; D007531:Isoflurophate / Q000494:pharmacology; D015609:Organotechnetium Compounds / Q000378:metabolism*; D010091:Oximes / Q000378:metabolism; D011877:Radionuclide Imaging; D019690:Technetium Tc 99m Exametazime; D013696:Temperature
D015609:Organotechnetium Compounds; D010091:Oximes; D007531:Isoflurophate; D019690:Technetium Tc 99m Exametazime; D004950:Esterases; C059659:technetium Tc 99m bicisate; D003545:Cysteine