Abstract
1352
Objectives Previous studies with dipicolylamine-Zn coordination complexes (DPA-Zn) labeled with either radioisotopes or optical fluorophores demonstrated promises in targeting phosphatidylserine (PS) of apoptotic cells with high affinity and specificity. Our aim was to compare the in vitro uptake difference of two 18F-DPA-Zn tracers, labeled with two different prosthetic groups, in cancer cells pretreated with camptothecin (CTP).
Methods DPA was labeled with N-succinimidyl 4-18F-fluorobenzoate (18F-SFB) and Al18F and then complexed with zinc nitrate. Human leukemia U937 cells were incubated with CTP (0, 25, 50, and 500 nM) for 24 h, respectively. Three µCi of each tracer was added to each well and incubated for 1 h at 37 oC. For blocking experiment, 50 µg DPA-Zn was added to each well for 15 min prior to the addition of each tracer (n=4). Cells were harvested, washed, and then counted for F-18 radioactivity. % uptake was calculated by counts in cells/total counts. The degree of cell apoptosis was measured by flow cytometry using a commercial annexin-V/PI kit.
Results The degree of cell apoptosis increased proportionally over CTP concentration- 2.67±1.05, 18.37±2.78, 62.73±4.25, 89.99±7.36 % for 0, 25, 50, and 500 nM of CTP, respectively. The uptake increased in a dose-dependent manner over CTP concentration-1.78±0.10, 2.71±0.24, 3.61±0.46 and 3.41±0.40 for 18F-Al-DPA-Zn, and 2.53±0.36, 3.11±0.21, 3.57±0.20, 3.81±0.14 for 18F-FB-DPA-Zn, respectively. The ratio of maximal uptake over the control group was 2.0 vs. 1.5, and the uptake was reduced to 61% and 47% after co-incubation with cold DPA-Zn for 18F-Al-DPA-Zn and 18F-FB-DPA-Zn, respectively.
Conclusions : Our preliminary data showed that at least 50% uptake of these two F-18 labeled PET tracers was due to specific binding to PS. 18F-Al-DPA-Zn might be slightly more sensitive than 18F-FB-DPA-Zn in targeting apoptosis, indicating a possible effect of prosthetic groups.