title: Effects of lithium gammalinolenate on the perfusion of liver and pancreatic tissues in pancreatic cancer.
abstract: Because of its poor prognosis, new modalities to treat pancreatic cancer are highly welcome. Gammalinolenate (GLA) has been shown to possess antitumor activity on various human cancer cell lines in vitro and some evidence has been found of its modulative activity on tubulin active agents, such as vinca alkaloids. GLA treatment is thought to change the penetration and distribution of chemotherapeutic agents in pancreatic tumor tissue. The in vivo effects of GLA are widely unknown. This is the first study on the modulation effects of both oral or intravenous GLA on blood perfusion in vivo. We analysed tissue perfusion prior to treatment and on the 10th day of GLA treatment in patients with pancreatic cancer. Dynamic gamma imaging was performed for 20 minutes after Tc-99m-MIBI injection, and the whole body was scanned after the dynamic study and at 4 hours. Half-lives in liver, left kidney, spleen, pancreas and tumor were recorded using a developed macro program for background corrected geometric mean data from irregular region of interests. Half-lives in the liver did not change due to oral GLA treatment, but they decreased dramatically in two of three patients after i.v. GLA treatment. Additionally, individual changes were observed in pancreatic half-lives, as in four out of five cases the half-life increased and in one case it decreased. No major changes were observed in kidney and spleen half-lives. GLA treatment had no effects on the blood brain barrier. This technique demonstrates perfusion in salivary glands, thyroid, lungs, heart, spleen, kidneys, muscles, spine and bladder, but no changes in perfusion could be detected due to GLA treatment. However, qualitatively enhanced blood flow through the pancreatic tumor was observed. In all patients irrespective of the route of administration of GLA, the organ-to-background ratios in liver decreased. The effect is, however, smallest after oral dosing. The pancreas-to-background ratio was increased in 3/5 patients, these patients exhibited stabilized disease. In a patient with large liver metastases the pancreas-to-background ratio decreased, and she showed a rapid disease progression during GLA therapy. The change in the pancreatic uptake was inversely proportional to the change in CA 19-9 concentration. Our results indicate the that GLA treatment dramatically changes tissue perfusion, especially in liver and pancreatic tumors, even at low doses, and these changes may predict response to GLA therapy.
authors.affiliation: Department of Oncology, Helsinki University Central Hospital, Finland.
authors.forename: K J
authors.initials: KJ
authors.lastname: Kairemo
authors.forename: A P
authors.initials: AP
authors.lastname: Jekunen
authors.forename: E T
authors.initials: ET
authors.lastname: Korppi-Tommola
authors.forename: S O
authors.initials: SO
authors.lastname: Pyrhönen
mesh_terms: D000284:Administration, Oral; D000368:Aged; D001812:Blood-Brain Barrier / Q000187:drug effects; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008099:Liver / Q000098:blood supply / Q000000981:diagnostic imaging / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000098:blood supply / Q000000981:diagnostic imaging / Q000187:drug effects*; D010190:Pancreatic Neoplasms / Q000098:blood supply*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D012039:Regional Blood Flow / Q000187:drug effects; D017256:Technetium Tc 99m Sestamibi; D017965:gamma-Linolenic Acid / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D019275:Radiopharmaceuticals; D017965:gamma-Linolenic Acid; D017256:Technetium Tc 99m Sestamibi