Fross R D, Warnke P C, Groothuis D R
Department of Neurology, Northwestern University Medical School, Evanston Hospital, Illinois 60201.
J Neurooncol. 1991 Dec;11(3):185-97. doi: 10.1007/BF00165526.
We used double-label quantitative autoradiography to measure blood flow (with 131I-iodoantipyrine) and blood-to-tissue transport of 14C-alpha aminoisobutyric acid, AIB) in thirteen 9L gliosarcomas transplanted intracerebrally into Fischer-344 rats. Microscopically, the typical pattern of 9L tumor growth was observed: a solid central tumor mass surrounded by extensive perivascular invasion. The averaged mean whole tumor transfer constant, K, of AIB in the 9L tumors was 33 +/- 15 (+/- SD) microliters/g/min. The averaged mean value of blood flow, F, was 72.2 +/- 27.3 ml/100 g/min. In brain around tumor (BAT), K (13 +/- 4 microliters/g/min) was lower than in the solid tumor, but was still 6-9 times that of tumor-free brain. F in BAT (115.9 +/- 64.6 ml/100 g/min) was comparable to values in tumor-free cortex in the same hemisphere. Values of K and F were used to calculate a net extraction fraction (En) for different regions of brain and tumor. The value of En of AIB in normal cortex was 0.003, in BAT En was 0.02, and in whole tumor the value was 0.09. The delivery of water-soluble compounds in 9L brain tumors is limited by the permeability/surface area characteristics of the tumor capillaries. The properties of blood-to-tissue transport and blood flow of 11 different brain tumor models are compared, and discussed with regard to the choice of brain tumor models for drug delivery research. The 9L brain tumor model is comparable to other transplanted rat brain tumor models, although the extent of tumor cell invasion into BAT makes this model distinctive. However, with regard to blood-to-tissue transport the 9L model differs from autochthonous models and transplanted human glioma models. We discuss guidelines for selecting brain tumor models with which to study the problem of drug delivery to brain tumors.
我们采用双标记定量放射自显影法，在13只移植了9L胶质肉瘤的Fischer-344大鼠脑内，测量血流量（使用131I-碘安替比林）以及14C-α-氨基异丁酸（AIB）的血-组织转运情况。显微镜下，观察到9L肿瘤典型的生长模式：中央为实体瘤块，周围有广泛的血管周围浸润。9L肿瘤中AIB的平均全肿瘤转运常数K为33±15（±标准差）微升/克/分钟。血流量F的平均值为72.2±27.3毫升/100克/分钟。在肿瘤周围脑组织（BAT）中，K（13±4微升/克/分钟）低于实体瘤，但仍为无瘤脑组织的6 - 9倍。BAT中的F（115.9±64.6毫升/100克/分钟）与同一半球无瘤皮质的值相当。利用K和F值计算脑和肿瘤不同区域的净摄取分数（En）。正常皮质中AIB的En值为0.003，BAT中为0.02，全肿瘤中为0.09。9L脑肿瘤中水溶性化合物的递送受肿瘤毛细血管通透性/表面积特性的限制。比较了11种不同脑肿瘤模型的血-组织转运和血流量特性，并就药物递送研究中脑肿瘤模型的选择进行了讨论。9L脑肿瘤模型与其他移植大鼠脑肿瘤模型相当，尽管肿瘤细胞侵入BAT的程度使该模型具有独特性。然而，在血-组织转运方面，9L模型与原发性模型和移植人胶质瘤模型不同。我们讨论了选择脑肿瘤模型以研究向脑肿瘤给药问题的指导原则。
