Blood flow dependence of the intratumoral distribution of peripheral benzodiazepine receptor binding in intact mouse fibrosarcoma
Blood flow dependence of the intratumoral distribution of peripheral benzodiazepine receptor binding in intact mouse fibrosarcoma
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DOI：
10.1016/j.nucmedbio.2006.08.004
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发表时间：
2006-11-01
影响因子：
3.1
通讯作者：
Inoue, Osamu
中科院分区：
文献类型：
--
作者：
Amitani, Misato;Zhang, Ming-Rong;Inoue, Osamu
[C-11]AC-5216 结合是一种新型外周苯二氮卓受体 (PBR) 配体，通过体外和体内放射自显影检查小鼠纤维肉瘤模型的肿瘤内分布。 [C-11]AC-5216 在体内肿瘤中的区域分布具有显着的异质性； [C-11]AC-5216 的摄取在肿瘤外缘相对较高，在中心区域较低。相反，注射[C-11]AC-5216和大量未标记的PK11195后获得的图像显示出相对均匀的分布，表明[C-11]AC-5216摄取代表与PBR的特异性结合。还使用纤维肉瘤切片获得了 [C-11]AC-5216 结合的体外放射自显影图，该切片与用于检查体内结合的切片相同。体外放射自显影结合图像显示均匀分布，并且在体内和体外图像之间观察到 [C-11]AC-5216 的瘤内分布存在显着差异。通过双重放射自显影技术获得的[C-11]AC-5216摄取的体内图像与[C-14]碘安替比林摄取的体内图像相比，以评估血流的影响，揭示了两种示踪剂相似的瘤内分布。这些结果表明，从血浆到肿瘤的递送过程可能是纤维肉瘤模型中 PBR 结合体内肿瘤内分布的限速步骤。 (c) 2006 Elsevier Inc. 保留所有权利。
The intratumoral distribution of [C-11]AC-5216 binding, a novel peripheral benzodiazepine receptor (PBR) ligand, was examined by autoradiography both in vitro and in vivo using a murine fibrosarcoma model. The regional distribution of [C-11]AC-5216 in a tumor in vivo was significantly heterogeneous; the uptake of [C-11]AC-5216 was comparatively higher in the outer rim of the tumor and was lower in the central area. In contrast, the images obtained following the injection of [C-11]AC-5216 with a large amount of nonlabeled PK11195 showed a relatively homogeneous distribution, suggesting that [C-11]AC-5216 uptake represented specific binding to PBRs. In vitro autoradiograms of [C-11]AC-5216 binding were also obtained using the section of the fibrosarcoma that was the same as that used to examine in vivo binding. In vitro autoradiographic binding images showed homogeneous distribution, and significant discrepancies of the intratumoral distribution of [C-11]AC-5216 were observed between in vivo and in vitro images. The in vivo images of [C-11]AC-5216 uptake, compared with those of [C-14]iodoantipyrine uptake, obtained by dual autoradiography to evaluate the influence of blood flow revealed the similar intratumoral distributions of both tracers. These results indicate that the delivery process from the plasma to the tumor might be the rate-limiting step for the intratumoral distribution of PBR binding in vivo in a fibrosarcoma model. (c) 2006 Elsevier Inc. All rights reserved.