RADIOLABELED FLUOROMISONIDAZOLE AS AN IMAGING AGENT FOR TUMOR HYPOXIA
RADIOLABELED FLUOROMISONIDAZOLE AS AN IMAGING AGENT FOR TUMOR HYPOXIA
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DOI：
10.1016/0360-3016(89)90146-6
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发表时间：
1989-11-01
影响因子：
7
通讯作者：
KROHN, KA
中科院分区：
文献类型：
--
作者：
RASEY, JS;KOH, WJ;KROHN, KA
用H-3或F-18标记的氟咪唑已被测试为体外缺氧细胞和体内啮齿动物和自发性犬肿瘤的定量探针。在体外V-79、EMT-6（UW）、RIF-1和犬骨肉瘤细胞中，相对于缺氧条件下的结合，50 μ M [H-3]Fluoromisonidazole的结合被1000-2000 ppm O2抑制50%。与标记药物孵育3小时后，4种细胞类型的缺氧/好氧结合比范围为12至27。注射后4小时，[H-3]氟咪唑在估计缺氧分数> 30%的大KHT肿瘤（400-600 mm 3）中的保留大于估计缺氧分数为7- 12%的较小肿瘤（50-200 mm 3）。估计缺氧分数为1.5%的RIF-1肿瘤保留了最少的标记，肿瘤：血液比率范围为1.7至1.9。自发性狗骨肉瘤成像飞行时间正电子发射断层扫描仪长达5小时后注射[F-18]氟咪唑。分析图像中的感兴趣区域，可以创建动态组织时间活性曲线，并计算组织吸收（cpm/g），这些值与血浆中的放射性进行比较。在所有情况下，在注射后3至5小时，某些肿瘤区域中的保留超过血浆和正常组织（如肌肉或脑）中的保留。肿瘤对氟咪唑的摄取是不均匀的，同一肿瘤不同部位的最大与最小摄取比值高达4。肿瘤：血浆值范围为0.28 - 2.02。氟咪唑滞留的氧依赖性在各种细胞类型中是相似的，并且在完全放射生物学缺氧和部分敏化之间的过渡中被O2水平抑制50%。[F-18]氟咪唑在自发性犬肿瘤中注射后不同时间的定量区域成像为人类肿瘤不同区域中氧依赖性药物滞留的成像和建模奠定了基础。
Fluoromisonidazole labeled with H-3 or F-18 has been tested as a quantitative probe for hypoxic cells in vitro and in rodent and spontaneous dog tumors in vivo. In V-79, EMT-6(UW), RIF-1, and canine osteosarcoma cells in vitro, the binding of 50 .mu.M [H-3]Fluoromisonidazole was 50% inhibited by 1000-2000 ppm O2, relative to binding under anoxic conditions. After a 3 hr incubation with labeled drug, the anoxic/oxic binding ratios ranged from 12 to 27 for the four cell types. Retention of [H-3]fluoromisonidazole 4 hr after injection was greater in large KHT tumors (400-600 mm3) with an estimated hypoxic fraction > 30%, than in smaller tumors (50-200 mm3) with an estimated hypoxic fraction of 7-12%. RIF-1 tumors, with an estimated hypoxic fraction of 1.5%, retained the least label, with tumor: blood ratios ranging from 1.7 to 1.9. Spontaneous dog osteosarcomas were imaged with a time of flight positron emission tomograph for up to 5 hr following injection of [F-18] fluoromisonidazole. Analysis of regions of interest in images allowedcreation of dynamic tissue time activity curves and calculation of tissue uptake in cpm/gram. These values were compared to radioactivity in plasma. In all cases, retention in some tumor regions exceeded that in plasma and in normal tissue, such as muscle or brain, by 3 to 5 hr post injection. Uptake of fluoromisonidazole in tumors was heterogeneous, with ratios of maximum to minimum uptke as high as 4 in different regions of interest in the same tumor. Tumor:plasma values ranged from 0.28 to 2.02. The oxygen dependency of fluoromisonidazole retention was similar in a variety of cell types and was 50% inhibited by O2 levels in the transition between full radiobiological hypoxia and partial sensitization. The quantitative regional imaging of [F-18] fluoromisonidazole in spontaneous canine tumors at varying times post-injection lays the basis for imaging and modeling of oxygen-dependent drug retention in different regins of human neoplasms.