EFFECTS OF LITHIUM GAMMALINOLENATE ON THE PERFUSION OF LIVER AND PANCREATIC TISSUES IN PANCREATIC-CANCER

Because of its poor prognosis, new modalities to treat pancreatic canc er are highly welcome. Gammalinolenate (GLA) has been shown to possess antitumor activity on various human cancel cell lines in vitro and so me evidence has been found of its modulative activity on tubulin activ e agents, such as vinca alkaloids. GLA treatment is thought to change the penetration and distribution of chemotherapeutic agents in pancrea tic tumor tissue. The in vivo effects of GLA are widely unknown. This is the first study on the modulation effects of both oral or intraveno us GLA on blood perfusion in vivo. We analysed tissue perfusion prior to treatment and on the 10th day of GLA treatment in patients with pan creatic cancer. Dynamic gamma imaging was performed for 20 minutes aft er Tc-99m-MIBI injection, and the whole body was scanned after the dyn amic study and at 4 hours. Half-lives in liver; left kidney spleen, pa ncreas and tumor were recorded using a developed macro program for bac kground corrected geometric mean data from irregular region of interes ts. Half-lives in the liver did not change due to oral GLA treatment, but they decreased dramatically in two of three patients after iv. GLA treatment. Additionally, individual changes were observed in pancreat ic half-lives, as in four out of five cases the half-life increased an d in one case it decreased. No major-changes were observed in kidney a nd spleen half-lives. CLA treatment had no effects on the blood brain barrier. This technique demonstrates perfusion in salivary glands, thy roid, lungs, heart, spleen, kidneys, muscles, spine and bladder; but n o changes in perfusion could be detected due to GLA treatment. However , qualitatively enhanced blood flow through the pancreatic tumor was o bserved. In all patients irrespective of the route of administration o f GLA, the organ-to-background ratios in liver decreased. The effect i s, however, smallest after oral dosing. The pancreas-to-background rat io was increased in 3/5 patients, these patients exhibited stabilized disease. In a patient with large liver metastases the pancreas-to-back ground ratio decreased, and she showed a rapid disease progression dur ing GLA therapy. The change in the pancreatic uptake was inversely pro portional to the change in CA 19-9 concentration. Our results indicate the that GLA treatment dramatically changes tissue perfusion especial ly in liver and pancreatic tumors, even at low doses, and these change s may predict response to GLA therapy.