Chang D, Jenkins S A, Grime S J, Nott D M, Cooke T
University Departments of Surgery, Royal Liverpool Hospital, UK.
Br J Cancer. 1996 Apr;73(8):961-5. doi: 10.1038/bjc.1996.188.
The effect of degradable starch microspheres (DSM) on the intrahepatic distribution of a low molecular weight marker, 99Tcm-labelled methylene diphosphonate (MDP), was studied in rats with hypovascular HSN liver tumours. MDP was injected regionally, via the hepatic artery, alone or co-administered with DSM, with or without subsequent occlusion of either the hepatic artery or the portal vein. Tumour vascularity was measured with 57Co-labelled microspheres. Co-injection with DSM immediately significantly increased hepatic retention of marker in both tumour (T) (median 22.40 (range 16.82-39.58)% injected dose) and normal liver (N) (9.08 (4.85-12.59) %ID) the greater effect seen in T (P < 0.01). After DSM degradation, very little MDP remained in N (0.61 (0.28-1.40) %ID) but there was significant retention in T (10.01 (6.73-20.28) %ID, P < 0.01). Clamping the hepatic artery had minimal effect on the retention of MDP when administered alone. Regional injection of 16.5 microM 57Co microspheres resulted in a N:T ratio of 2.25:1. Concomitant injection of the 40 microM DSM was 57Co microspheres reversed this ratio to 1:2. The results indicate that DSM selectively enhances the retention of MDP to a hypovascular hepatic tumour, not by causing intra-tumour stasis, but by directing a greater arterial flow to hypovascular areas in the liver.
在患有低血供HSN肝肿瘤的大鼠中,研究了可降解淀粉微球(DSM)对低分子量标记物99Tcm标记的亚甲基二膦酸盐(MDP)肝内分布的影响。MDP通过肝动脉局部注射,单独注射或与DSM共同给药,肝动脉或门静脉随后进行或不进行闭塞处理。用57Co标记的微球测量肿瘤血管生成。与DSM共同注射立即显著增加了标记物在肿瘤(T)(中位值为注射剂量的22.40(范围16.82 - 39.58)%)和正常肝脏(N)(9.08(4.85 - 12.59)%ID)中的肝内滞留,在T中观察到的效果更明显(P < 0.01)。在DSM降解后,N中几乎没有MDP残留(0.61(0.28 - 1.40)%ID),但T中仍有显著滞留(10.01(6.73 - 20.28)%ID,P < 0.01)。单独给予MDP时,夹闭肝动脉对其滞留的影响最小。局部注射16.5 microM 57Co微球导致N:T比例为2.25:1。同时注射40 microM DSM与57Co微球可将该比例逆转至1:2。结果表明,DSM选择性地增强了MDP在低血供肝肿瘤中的滞留,不是通过引起肿瘤内淤滞,而是通过引导更多的动脉血流至肝脏的低血供区域。