[Experimental studies on the dynamics of anticancer agents in transcatheter arterial chemo-embolization. Magnetic resonance imaging using emulsions containing lipiodol and Gd-DTPA].
Transcatheter arterial chemo-embolization with lipiodol and anticancer agents (LP-TACE) is a highly effective therapeutic method for treating liver cancer. It has been difficult, however, to evaluate how lipiodol, an oil, and anticancer agents dissolved in an aqueous contrast medium are retained in tumors. This paper reports the study on the dynamics of anticancer agents administered in LP-TACE both in vitro and in tumor-bearing animals using emulsions produced by mixing lipiodol and adriamycin (ADM) dissolved in Gd-DTPA. The results were as follows. 1) ADM was dissolved in contrast mediums (60% Urografin and Gd-DTPA) and each solution was emulsified by mixing with lipiodol. The emulsion separated into two distinct layers 5 min. after mixing. From this observation it is guessed that lipiodol and anticancer agents also separate in tumors after administration in LP-TACE. 2) Rabbits with VX2 carcinoma implanted in their lower limbs were treated by chemo-embolization and subjected to serial observations for changes in signals on MRI. The signal intensity markedly increased, persisting until one week after administration, when the tumor was resected. This change may have been owing to Gd-DTPA retained in the tumor, indicating that the anticancer agent is not washed out, even after separating from lipiodol, but is retained in the tumor. 3) When ADM was dissolved in Gd-DTPA and intraarterially infused without being mixed with lipiodol, the intensity of the signal on MRI was the same as that in LP-TACE immediately after the administration, and gradually decreased thereafter. This result indicates earlier washout of the anticancer agent when administered without being combined with lipiodol. Quantitative analysis of the tumor resected one week after the treatment also revealed ADM levels with less than 10% of those in LP-TACE, suggesting the possibility of estimating intratumoral concentration of anticancer agents. This was evaluated on the basis of the signal intensity in the tumor using MRI. 4) A comparison of lipiodol accumulation on CT and signal changes induced by Gd-DTPA on MRI suggested that even after separation from lipiodol, the anticancer agent extends to microvessels in the interior part of the tumor.
Ishio
M
M
Second Department of Surgery, Nippon Medical School, Japan.
D000818:Animals; D003974:Diatrizoate Meglumine; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004621:Embolization, Therapeutic; D004655:Emulsions; D019786:Gadolinium DTPA; D007459:Iodized Oil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging; D009336:Necrosis; D009374:Neoplasms, Experimental / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D009942:Organometallic Compounds; D004369:Pentetic Acid; D011817:Rabbits
D004655:Emulsions; D009942:Organometallic Compounds; D003974:Diatrizoate Meglumine; D004369:Pentetic Acid; D007459:Iodized Oil; D004317:Doxorubicin; D019786:Gadolinium DTPA