Steve Y Cho MD, Presenter: Nothing to Disclose

Richard Leo Wahl MD, Abstract Co-Author: Nothing to Disclose

Selectively increasing FDG tumor uptake could improve the diagnostic accuracy of PET imaging and allow for visualization of smaller tumors. Dipyridamole (DIP) exhibits a wide variety of biologic effects, most purine related, but its effect on tumor FDG uptake has not been reported in the literature. We report an intriguing observation on the effect of DIP on intracellular FDG uptake in various human tumor cells lines in vitro.

Ovarian adenocarinoma (SKOV-3), glioma (U87, U251), and mammary adenocarcinoma (MN-1 and MDD2; MCF-7 derived cells [gift of Dr. Galmarini]) cells were evaluated. Cells were pre-treated in serum free RPMI 1640 media with low physiologic glucose (0.8 g/L) either alone, or with addition of dipyridamole, for 1 hour followed by exposure to 0.1 mCi of [3H]FDG for 75 minutes, at 37ºC. Cells are washed with PBS then collected for measurement in a scintillation counter. Statistical significance was evaluated using the Student t-test.

([3H]FDG uptake data are reported as dpm/106 cells) [3H]FDG uptake in SKOV-3 cells was 3,633; pre-treatment of SKOV-3 cells with 10μM and 100μM DIP significantly increased uptake by 14.2% to 4,148 (p<0.047), and 82.9% to 6,645 (p<0.00086), respectively. [3H]FDG uptake in U87 cells was 9,599; pre-treatment of U87 cells with 10μM significantly increased uptake by 59.3% to 15,292, (p<0.000056). [3H]FDG uptake in U251 cells was 54,848; pre-treatment of U251 cells with 10μM significantly increased uptake by 38.6% to 75,995, (p<0.0015). [3H]FDG uptake in MN-1 cells was 18,948; pre-treatment of MN-1 cells with 10μM significantly increased uptake by 29.8% to 24,588, (p<0.011). [3H]FDG uptake in MDD2 cells was 26,529; pre-treatment of MDD2 cells with 10μM significantly increased uptake by 14.4% to 30,336, (p<0.022).

[3H]FDG uptake was significantly increased in several tumor cell lines pre-treated with DIP in comparison to untreated cells. We report a novel finding that FDG uptake in tumor cells can be augmented in vitro by pre-treatment with DIP. The mechanism of action is unclear, but likely through a purine pathway, and this observation warrants further evaluation in vivo for its selectivity.

R.L.W.: GE Medical Systems - Commercial Grants; GE Medical Systems – Honorarium; Philips – Honorarium; CPS Innovations – Honorarium; Cardinal Health – Honorarium; Nihon-Medi-Physics Corporation – Consultant; Threshold Pharmaceuticals – Consultant; National Cancer Institute – Research Support

Selectively increasing FDG tumor uptake could improve the diagnostic accuracy of PET imaging and allow for visualization of smaller tumors. Dipyridamole (DIP) exhibits a wide variety of biologic effects, most purine related, but its effect on tumor FDG uptake has not been reported in the literature. We report an intriguing observation on the effect of DIP on intracellular FDG uptake in various human tumor cells lines in vitro.

Ovarian adenocarinoma (SKOV-3), glioma (U87, U251), and mammary adenocarcinoma (MN-1 and MDD2; MCF-7 derived cells [gift of Dr. Galmarini]) cells were evaluated. Cells were pre-treated in serum free RPMI 1640 media with low physiologic glucose (0.8 g/L) either alone, or with addition of dipyridamole, for 1 hour followed by exposure to 0.1 mCi of [3H]FDG for 75 minutes, at 37ºC. Cells are washed with PBS then collected for measurement in a scintillation counter. Statistical significance was evaluated using the Student t-test.

([3H]FDG uptake data are reported as dpm/106 cells) [3H]FDG uptake in SKOV-3 cells was 3,633; pre-treatment of SKOV-3 cells with 10μM and 100μM DIP significantly increased uptake by 14.2% to 4,148 (p<0.047), and 82.9% to 6,645 (p<0.00086), respectively. [3H]FDG uptake in U87 cells was 9,599; pre-treatment of U87 cells with 10μM significantly increased uptake by 59.3% to 15,292, (p<0.000056). [3H]FDG uptake in U251 cells was 54,848; pre-treatment of U251 cells with 10μM significantly increased uptake by 38.6% to 75,995, (p<0.0015). [3H]FDG uptake in MN-1 cells was 18,948; pre-treatment of MN-1 cells with 10μM significantly increased uptake by 29.8% to 24,588, (p<0.011). [3H]FDG uptake in MDD2 cells was 26,529; pre-treatment of MDD2 cells with 10μM significantly increased uptake by 14.4% to 30,336, (p<0.022).

[3H]FDG uptake was significantly increased in several tumor cell lines pre-treated with DIP in comparison to untreated cells. We report a novel finding that FDG uptake in tumor cells can be augmented in vitro by pre-treatment with DIP. The mechanism of action is unclear, but likely through a purine pathway, and this observation warrants further evaluation in vivo for its selectivity.

R.L.W.: GE Medical Systems - Commercial Grants; GE Medical Systems – Honorarium; Philips – Honorarium; CPS Innovations – Honorarium; Cardinal Health – Honorarium; Nihon-Medi-Physics Corporation – Consultant; Threshold Pharmaceuticals – Consultant; National Cancer Institute – Research Support

Cho, S, Wahl, R, Augmentation of FDG Uptake in Tumor Cells Treated with Dipyridamole.  Radiological Society of North America 2005 Scientific Assembly and Annual Meeting, November 27 - December 2, 2005 ,Chicago IL. http://archive.rsna.org/2005/4418657.html