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KMID : 0350519930460020701
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Journal of Catholic Medical College
1993 Volume.46 No. 2 p.701 ~ p.711
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Biodistribution of In=111-Platelet in Thrombocytopenia Induced by Granulocyte Macrophage-Colony Stimulating Factor
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Abstract
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There has been tremendous advances in DNA cloniong technology to produce a variety of hematopoietic growith factors including granulocyte macrophage-colony stimulating factor (CM-CSF) which are now clinically available. Because GM-CSF greatly
stimulates
the production of white blood cells, it can be used to reduce the morbidity associated with chemotherapy or cancer-related myelosuppression, by decreasing the incidence of infectious complications. Unfortunately, however, it reduces the platelet
counts
as a side effect of GM-CSF treatment.
When canine GM-CSF (Cgm-csf) is administered to normal dogs there is an increase in peripheral blood neutrophils and predictable dose-dependent decrease in platelet counts. To study the mechanism of cGM-CSF-induced throbocytopenia, the
biodistribution
of radiolabeled platelets was evaluated in three normal dogs with autologous In-111-platelets and quantitative gamma camera imaging before and after administration of cGM-CSF.
Autologous platelets were separated and labeled with In-111-oxine using the standard technique, After intravenous injection of In-111-platelets, initial data were recorded for 90 minutes followed by whole body imaging at 2, 24, and 48 hours.
Hepatic and
splenic uptake of labeled platelets were quantitated with geographic mean technique and transmission attenuation scan in terms of % of injected dose.CBC and life span of the platelets were extimated as well as recovery at 30 minutes.
One week after the baseline study, subcutaneous injection of cGM-CSF (50 μg/kg/day, b.i.d., for 14 days) was started and a second set of the same study was performed at 7th. Day of cGM-CSF administration.
Peripheral platelet counts decreased during the first day of cGM-CSF and reached a nadir in 5 to 7 days which was 26% of the baseline. Peripheral whith blood cell counts increased 4 to 5 fold. During the administration of cGM-CSF hepatic uptake
of
In-111-platelets were markedly increased in all three dogs. Mean hepatic uptake of platelets at 2 hours was 2.2 times greater, going from 16.9% to 37.2% of injected dose after the injection of cGM-GSF. Splenic uptake of In-111-platelets (36% of
injected
dose) was unchanged by cGM-CSF. The initial dynamic study indicated that the uptake of platelets in the liver was increased from the early phase of the study after the administration ofcCGM-CSF. Recovery of the platelets was decreased after the
administration of cGM-CSF, from 61% to 35%, and platelet life span was also decreased from 3.9 days to 1.6 days after cGM-CSF treatment.
Bone marrow uptake of platelets was remarkably increased on delayed scan in two dogs.
We concluded that. cGM-CSF-induced thrombocytopenia is associated with markedly increased hepatic uptake of the platelets and also to lesser extent, with bone marrow uptake. We think this might be cause by enhanced RES activity and/or cGM-CSF
induced
changes of platelet morphology or surface antigens which results in their early removal. Experiments are still under way to study these possibilities. μ
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