ISSN:
1619-7089
Keywords:
Indium-111 labelled lymphocytes
;
Fluorine-18
;
fluorodeoxyglucose
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Since lymphocytes continue to proliferate and divide in vivo, it is important to determine the fate of a radionulide following lymphocyte labelling. Using the mixed lymphocyte reaction (MLR), we induced indium-111 labelled lymphocytes from a specific in-bred rat strain (AS) to divide and then observed the subsequent111In distribution between cells and supernatant. L10 and L12.4 cells, which are allospecific CD4+ T lymphocytes from the AS rat, were stimulated in the MLR by antigen-presenting cells from the August rat, a different strain. We labelled L10 or L12.4 lymphocytes on day 0, the first day of the stimulation cycle, and continued to culture the lymphocytes in vitro. The proliferation of the cells was estimated according to their increase in number. The distribution of111In between cell and supernatant fractions and between viable and dead (but intact) cells was measured in the cell suspension each day after labelling. The metabolic activity of111In-labelled lymphocytes was compared with control cells by measuring their uptake of fluorine-18 fluorodeoxyglucose ([18F]FDG).111In-labelled lymphocytes showed a poor proliferative response compared with control cells 24–48 h after labelling but increased in number after this time. From 24 to 72 h, about 70% of111In was in the supernatant but only about 5%–10% was associated with intact dead cells. These dead cells tended to retain their111In, losing less than 30% per day, suggesting that111In in the supernatant was the result of active elimination from viable cells. Moreover, 24 h after culture, considerably more111In was associated with viable than with dead lymphocytes, although over the next few days this distribution reversed.111In-labelled lymphocytes took up more [18F]FDG than control cells at 24 h but not at 0 or 72–96 h; the maximum [18F]FDG uptake coincided with the greatest reduction in cell number. Furthermore, [18F]FDG uptake correlated with the initial111In burden in lymphocytes labelled with111In 24 h previously. The results are consistent with active elimination of111In by111In-labelled lymphocytes. The energy requirements for this are diverted away from cell division, thereby increasing the probability of cell death. As lymphocytes become111In deplete, they recover their capacity to proliferate and their risk of death decreases. These findings have important implications for111In-labelled lymphocyte scintigraphy, suggesting that cells remaining viable immediately after labelling will either subsequently die or alternatively eliminate the label.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01267679
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