RT Journal Article
SR Electronic
T1 Cancer cell killing by σ-ligands and sTRAIL: Monitoring synergy with PET
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1551
OP 1551
VO 50
IS supplement 2
A1 Anna Rybczynska
A1 Marco De bruyn
A1 Philip Elsinga
A1 Rudi Dierckx
A1 Wijnand Helfrich
A1 Aren van Waarde
YR 2009
UL http://jnm.snmjournals.org/content/50/supplement_2/1551.abstract
AB 1551 Objectives We examined whether sub-toxic amounts of haloperidol (HAL) or rimcazole (RIM), Σ-ligands which potentiate the anti-tumor actions of cytostatics, and sTRAIL (a tumor-selective pro-apoptotic protein) synergistically kill human cancer cells. We assessed early metabolic responses in tumor and healthy cells and we determined if tracer uptake reflects synergistic cell killing. Methods A375M (human melanoma) and HUVEC (human umbilical cord endothelial) cells were incubated (24h) with sTRAIL, RIM, RIM + sTRAIL, HAL or HAL+ sTRAIL. Cytotoxicity was assessed by cell counting. Metabolism was quantified using 18F-FDG, 18F-FLT and 11C-choline. Cellular ATP levels were measured and cell cycle analysis was performed. A cooperativity index (CI) < 0.9 indicates synergy. Results Σ-ligands and sTRAIL synergized in A375M (CIHAL=0.51; CIRIM=0.71) but not in HUVEC (100% survival). Σ-ligand-treated A375M cells synchronized at G1/G0 in a dose-dependent manner, addition of sTRAIL did not significantly change the G1/G0 population. Cellular ATP decreased by 37%, 45-54% and 88-92% after sTRAIL, Σ-ligand and co-treatment, respectively. FDG uptake reflected synergistic killing (CIHAL=0.54; CIRIM=0.55), in contrast to FLT or choline. Conclusions Combination therapy with Σ-ligands and sTRAIL resulted in synergistic decreases of cell number and in corresponding increases of cellular glucose transport. However, FLT or choline uptake did not reflect cooperativity.