Effects of a Tc-99m-labeled murine immunoglobulin M antibody to CD15 antigens on human granulocyte membranes in healthy volunteers

An injectible, Tc-99m-labeled, murine immunoglobulin M antibody to stage-sp ecific embryonic antigen-1 has been developed that can localize infections by binding to CD15 glycoproteins expressed on the cell membranes of human g ranulocytes in vivo after systemic administration. The purpose of this stud y was to measure its clinical effects on healthy people. Methods: Multiple blood samples were aspirated before and after the intravenous administratio n of about 125 mu g antibody labeled with similar to 370 MBq (10.0 mCi) Tc- 99m in 10 healthy human volunteers. Complete blood cell counts were perform ed at each time point. Whole-body scans were acquired contemporaneously wit h a dual-head gamma camera. The fraction of the administered dose at each t ime point was quantified in 18 regions of interest. Statistical analyses in cluded paired ttests. Results: Administration was associated with a transie nt 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 wa s always reached 15-20 min after administration. There was full recovery wi th 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 circulatin g granulocytes, which fell from 5.7 +/- 2.1 to 3.2 +/- 1.3 x 10(3)/mu L blo od. The drop paralleled a decrease in the percentage of whole blood radioac tivity 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 am ount of radioactivity within the liver and the spleen. Recovery was associa ted with a decrease in hepatosplenic radioactivity. No evidence of cell des truction or agglutination could be detected. Conclusion: This study confirm ed that administration of this radiolabeled antibody is associated with a t ransient decrease in the number of circulating granulocytes. However, there also seems to be a secondary hemodilutionlike effect on all blood componen ts that has not been reported previously. The effect appears to be clinical ly silent and very short-lived.