Blood flow dependence of the intratumoral distribution of peripheral benzodiazepine receptor binding in intact mouse fibrosarcoma

Abstract 

The intratumoral distribution of [¹¹C]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 [¹¹C]AC-5216 in a tumor in vivo was significantly heterogeneous; the uptake of [¹¹C]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 [¹¹C]AC-5216 with a large amount of nonlabeled PK11195 showed a relatively homogeneous distribution, suggesting that [¹¹C]AC-5216 uptake represented specific binding to PBRs. In vitro autoradiograms of [¹¹C]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 [¹¹C]AC-5216 were observed between in vivo and in vitro images. The in vivo images of [¹¹C]AC-5216 uptake, compared with those of [¹⁴C]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.

Keywords: AC-5216, Peripheral benzodiazepine receptors, Intratumoral distribution, Autoradiography, In vivo, Blood flow