title: Effects of a 99mTc-labeled murine immunoglobulin M antibody to CD15 antigens on human granulocyte membranes in healthy volunteers.
abstract: An injectible, 99mTc-labeled, murine immunoglobulin M antibody to stage-specific embryonic antigen-1 has been developed that can localize infections by binding to CD15 glycoproteins expressed on the cell membranes of human granulocytes in vivo after systemic administration. The purpose of this study was to measure its clinical effects on healthy people.
  
  
  METHODS
  Multiple blood samples were aspirated before and after the intravenous administration of about 125 microg antibody labeled with approximately 370 MBq (10.0 mCi) 99mTc in 10 healthy human volunteers. Complete blood cell counts were performed at each time point. Whole-body scans were acquired contemporaneously with a dual-head gamma camera. The fraction of the administered dose at each time point was quantified in 18 regions of interest. Statistical analyses included paired t tests.
  
  
  RESULTS
  Administration was associated with a transient decrease in the concentration of red and white blood cells in the whole blood. The effect always began within 3 min of administration. Its nadir was always reached 15-20 min after administration. There was full recovery with mild overcompensation in about an hour. The hematocrit dropped by a mean of 3.8% (P<0.002), whereas the total white blood cell count fell 44.0%+/-3.1% (P<0.001). The effect was most pronounced on the number of circulating granulocytes, which fell from 5.7+/-2.1 to 3.2+/-1.3x10(3)/microL blood. The drop paralleled a decrease in the percentage of whole blood radioactivity bound to the white blood cell membranes, which peaked at 50.4%+/-7.6% at 3 min after injection and then fell to 26.1%+/-9.3% over the next 30+/-13.4 min before recovering to 40.7%+/-8.2% at 2 h. Image analysis showed that the effect was temporally associated with an increase in the amount of radioactivity within the liver and the spleen. Recovery was associated with a decrease in hepatosplenic radioactivity. No evidence of cell destruction or agglutination could be detected.
  
  
  CONCLUSIONS
  This study confirmed that administration of this radiolabeled antibody is associated with a transient decrease in the number of circulating granulocytes. However, there also seems to be a secondary hemodilutionlike effect on all blood components that has not been reported previously. The effect appears to be clinically silent and very short-lived.
authors.affiliation: Division of Nuclear Medicine, University of Pennsylvania, Philadelphia, USA.
authors.forename: P D
authors.initials: PD
authors.lastname: Mozley
authors.forename: M L
authors.initials: ML
authors.lastname: Thakur
authors.forename: A
authors.initials: A
authors.lastname: Alavi
authors.forename: T
authors.initials: T
authors.lastname: Smith
authors.forename: E D
authors.initials: ED
authors.lastname: Barraclough
authors.forename: P
authors.initials: P
authors.lastname: Wilding
authors.forename: B A
authors.initials: BA
authors.lastname: Rhodes
authors.forename: M
authors.initials: M
authors.lastname: Patel
authors.forename: A
authors.initials: A
authors.lastname: Mathur
authors.forename: P
authors.initials: P
authors.lastname: Li
mesh_terms: D000328:Adult; D000818:Animals; D001772:Blood Cell Count; D002462:Cell Membrane / Q000276:immunology; D005260:Female; D006098:Granulocytes / Q000166:cytology / Q000276:immunology*; D006400:Hematocrit; D006801:Humans; D007075:Immunoglobulin M / Q000494:pharmacology*; D007958:Leukocyte Count; D016256:Lewis X Antigen / Q000032:analysis*; D008297:Male; D051379:Mice; D008875:Middle Aged; D013667:Technetium / Q000494:pharmacology*
chemical_list: D007075:Immunoglobulin M; D016256:Lewis X Antigen; D013667:Technetium