In vitro human leukocyte labeling with (64)Cu: an intraindividual comparison with (111)In-oxine and (18)F-FDG.
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.


CONCLUSIONS
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.
Bhargava
Kuldeep K
KK
North Shore Long Island Jewish Health System, Manhasset and New Hyde Park, NY 11040, USA.
Gupta
Raj K
RK
Nichols
Kenneth J
KJ
Palestro
Christopher J
CJ
D000328:Adult; D002470:Cell Survival / Q000187:drug effects; D003301:Copper Radioisotopes / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds / Q000378:metabolism* / Q000494:pharmacology; D015125:Oxyquinoline / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D013194:Staining and Labeling / Q000379:methods*
D003301:Copper Radioisotopes; D009942:Organometallic Compounds; D019788:Fluorodeoxyglucose F18; C032950:indium oxine; D015125:Oxyquinoline