We investigated labeling human leukocytes [white blood cells (WBCs)] in vitro with copper-64 (Cu) comparing labeling efficiency, viability and stability of Cu-WBCs with (111)In-oxine (In) WBCs and (18)F-FDG (FDG) WBCs.
Methods: Leukocytes from 10 volunteers were labeled with Cu, In and FDG. Forty milliliters of venous blood was collected and leukocyte separation was performed according to standard methods. In-WBCs and FDG-WBCs were labeled according to published methods. For Cu-WBCs, tropolone initially was used as a single chelating agent. Because of poor intracellular Cu retention (54+/-4% at 3 h and 24+/-5% at 24 h), the fluorinated, membrane-permeable divalent cation chelator quin-MF was added. WBCs were incubated in 5 ml saline containing 100 microl of 1mM quin-MF/AM in 2% dimethyl sulfoxide and 74-185 MBq Cu-tropolone for 45 min at 37 degrees C. Labeling efficiencies; in vitro cellular viabilities at 1, 3 and 24 h; and in vitro stabilities at 1, 2, 3, 4 and 24 h (except FDG-WBCs) were determined.
Results: Mean Cu-WBCs (87+/-4%) and In-WBCs (86+/-4%) labeling efficiencies were comparable and were significantly higher than FDG-WBCs (60+/-19%, P<.001). Cell viabilities, similar at 1 h, were significantly higher for (64)Cu-WBCs at 3 and 24 h. Intracellular retention of activity was always significantly higher for In-WBCs than for Cu-WBCs and FDG-WBCs. At 24 h, intracellular retention was 88+/-4% for In-WBCs and 79+/-6% for Cu-WBCs.
Conclusion: Cu-WBC labeling efficiency and viability were comparable or superior to In-WBCs and significantly higher than FDG-WBCs. Although significantly more activity eluted from Cu-WBCs than from In-WBCs, Cu-WBC probably is adequate for imaging. These data suggest that further investigation of in vitro copper-64-labeled leukocytes for PET imaging of infection is warranted.