In vivo kinetics of 111indium-labelled autologous granulocytes following i.v. administration of granulocyte-macrophage colony-stimulating factor (GM-CSF).
Administration of both glycosylated and non-glycosylated recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) induces an immediate transient granulocytopenia of 1-3 hours' duration. In order to explore this phenomenon, granulocytes were labelled with 111Indium and the effect on the kinetics of granulocytes after administration of rhGM-CSF was studied in 10 previously untreated patients with malignant lymphoma. For both types and doses of rhGM-CSF, a significant and dramatic accumulation of the 111Indium-labelled granulocytes was observed in the lung within a few minutes after i.v. injection of rhGM-CSF. The accumulation of radioactivity coincided with the pronounced and transient granulocytopenia in peripheral blood. The 111Indium-labelled granulocytes later reappeared in the peripheral blood, indicating reversible pulmonary vascular margination of the granulocytes. Half-life of labelled granulocytes after reappearance was comparable to half-life values under normal conditions. The transient accumulation of granulocytes in the pulmonary vessels seems not to be of clinical importance in the management of patients, but it may to some degree explain previously described side-effects, such as transient hypoxemia ("first-dose" reaction) following administration of rhGM-CSF.
Hovgaard
D
D
Department of Hematology, Rigshospitalet, Copenhagen, Denmark.
Schifter
S
S
Rabøl
A
A
Mortensen
B T
BT
Nissen
N I
NI
D000380:Agranulocytosis / Q000139:chemically induced; D006031:Glycosylation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000493:pharmacokinetics / Q000494:pharmacology*; D006098:Granulocytes / Q000187:drug effects*; D006207:Half-Life; D006801:Humans; D007205:Indium Radioisotopes; D007275:Injections, Intravenous; D007958:Leukocyte Count; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008223:Lymphoma / Q000188:drug therapy; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology; D013154:Spleen / Q000378:metabolism; D013997:Time Factors
D007205:Indium Radioisotopes; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor