This study indicates that the distribution to tumor tissue was enhanced when [3H]TXL was administered as a macromolecular conjugate, and that free TXL was released and maintained within the tumor for a prolonged period. Thus, the antitumor activity of PG-TXL observed in preclinical studies may be attributed in part to enhanced tumor uptake of PG-TXL.

These results validate the idea that functional CT can help quantify the perfusion function of mature vessels but not changes in microvessel density in antiangiogenic therapy.

Comprehension of the structural and functional characteristics of the hepatic microcirculation can help improve the design, planning, and practice of imaging-guided treatment for hepatic tumors and for portal vein embolization (PVE). The hepatic microcirculation derives dual blood supply from the portal vein and the hepatic artery. The terminal portal venules directly connect to the hepatic sinusoids, but the terminal hepatic arterioles connect to arterioportal communications before entering the sinusoids: the peribiliary plexus, the terminal arteriosinus twigs, the vasa vasorum on the portal vein, and the direct arterioportal anastomosis. These communications play important roles in the balance of blood perfusion to the liver parenchyma and in controlling the blood supply to hepatic tumors and the anticipated remnant liver (in cases of PVE). At the microcirculatory level, various embolic agents present different distribution patterns. To further our understanding, iodized oil has been found to pass into the portal vein after hepatic arterial administration through the peribiliary plexus and subsequently traverses the sinusoids to enter the lungs and then the systemic circulation. Ultimately, a thorough knowledge of the host environment at the microcirculatory level is essential in developing strategies for both tumor treatment and for inducing liver regeneration.

To define the intrahepatic distribution of iodized poppyseed oil and its effect on the liver, hepatic artery embolization (HAE) was performed in five mice, 12 rats, four rabbits, and 21 pigs with the iodized oil alone or in combination with gelatin sponge powder (GSPow) in three rats or gelatin sponge particles (GSPs) in nine pigs. All mice, rats, and rabbits underwent radiography of the upper abdomen and in vivo microscopy of the hepatic periphery during and immediately after injection and 1, 4, and 24 hours later. All pigs underwent angiography before and after HAE as well as measurement of portal venous pressure before HAE and 15, 30, 45, and 60 minutes and 4 weeks after HAE. Follow-up radiographs were obtained in 18 pigs. HAE performed with the iodized oil only was well tolerated by the liver, even when high doses were used, likely because of continuous flushing of the sinusoids by high blood flow from peripheral arterioles. When HAE was performed with the iodized oil and GSPow, this blood flow ceased and necrosis developed. The degree of necrosis after HAE with the iodized oil in combination with GSPs was directly associated with the dose of iodized oil. HAE performed with GSPs only did not cause damage.

The dynamics of blood circulation in three experimental animal models of hepatic metastasis were investigated with in vivo microscopy. It was demonstrated that the tumor vasculature communicated with the portal venules and hepatic sinusoids that surrounded the tumors. The hepatic artery was not seen to connect to the tumors directly. However, it was demonstrated that arterial blood entered tumors through the portal venules and that the hepatic arterial flow entered the tumor without resistance, while blood from the portal vein met great resistance at the tumor border, with only small amounts entering the tumor. Interruption of either the hepatic artery or the portal vein did not result in cessation of the blood circulation in hepatic tumors. A reciprocal relationship between the hepatic arterial and portal venous supplies to hepatic tumors was suggested, and it was hypothesized that arterioportal communications play an important role in the arterial and portal venous supply of blood to hepatic tumors. A comprehensive understanding of the blood supply of hepatic tumors is important for improving clinical treatment of hepatic tumors.

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The results of this study validate the use of functional CT in the quantification of tumor perfusion after TAE and the reproducibility of such quantification measurements.

TAE of hepatic tumors results in the stimulation of angiogenesis in the residual viable tumor, which could have an adverse effect on the therapeutic efficacy of TAE.