원저 : 이종이식된 인체종양에서 KR - 30035 가 Tc - 99m MIBI 체내 분포에 미치는 영향으로 평가한 다약제내성 역전가능성 ( Orginal Articles : Reversal of Multidrug Resistance with KR - 30035 ; Evaluated with Biodistribution of Tc - 99m MIBI in Nude Mice Bearin () |
Author |
김정균(Jung Kyun Kim),이재태(Jae Tae Lee),이병호(Byung Ho Lee),최상운(Sang Woon Choi),유성은(Sung Eun Yoo),이상우(Sang Woo Lee),천경아(Kyung Ah Chun),안병철(Byeong Cheol Ahn),박재용(Jae Young Park),서장수(Jang Soo Suh),이규보(Kyu Bo Lee), |
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Abstract |
Purpose: KR-30035 (KR), a new MDR reversing agent, has been found to produce a similar degree of increased Tc-99m MIBI uptake in cultured tumor cells over-expressing mdr1 mRNA compared to verapamil (VP), with less cardiovascular effects. We assessed the MDR-reversing ability of KR in vivo, and effects of various doses of KR on MIBI uptake in nude mice bearing P-glycoprotein (P-gp) positive (+) and P-gp negative (-) human tumor xenografts. Methods: P-gp (+) HCT15/CL02 colorectal and P-gp (-) A549 non-small cell cancer cells were inoculated in each flank of 120 nude mice (20 mice x 6 groups). Group 1 (Grl) mice received 10mg/kg KR i.p. 3 times (x3) Gr2, 10mg/kg VP i.p. x3: Gr3, 10mg/kg KR i.p, x2 + 25mg/kg KR i.p. x1 Gr4, 10mg/kg KR i.p. x2 + 50mg/kg i.p. x1' Gr5, 10mg/kg KR i.p. x2 + 25mg/kg KR i.v. x1, GrC, controls. The mice were then injected with Tc-99m MIBI and sacrificed after 10 min, 30 min, 90 min and 240 min. Tumor uptake of MIBI (TU) in each group was compared. Results: TU in P-gp (+) and (-) tumors were both higher in Grl than Gr2. Washout rate between the 10 min and 4 hours was lower in Gr5 of P-gp (+) cell(0.93) than the control. Percentage increases in TU were higher in P-gp (+) than P-gp (-) tumors with all KR doses. Pgp (+) TU were highest at 10 min (173% of GrC) and persisted up to 240 min (144%) in Gr3. Larger doses of KR resulted in a lesser degree of increase in P-gp (+) TU at 10 min (130% in Gr4 and 117% in Gr5) and 30 min (178% 129%), but TU increased by time up to 240 min (177% 196%). Heart and lung uptakes were markedly increased in Gr4 and Gr5 at 10 and 30 min, likely due to cardiovascular effects. No mice died. Conclusion: These data further suggest that KR that has signiticantly lower cardiovascular toxicity than verapamil can be used as an active inhibitor of MDR. Even a relatively low dose of KR significantly increased Tc-99m MIBI uptake in P-gp (+) tumors in vivo. (Korean J Nucl Med 200135:168-184) |
Keyword |
KR - 30035 , Verapamil , Mutidrug resistance , Tc - 99m MIBI |
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