Lipiodol Solution Of ～(188)Re-labeled TDD Derivative As A Therapeutic Agent For Transhepatic Arterial Embolization In Rabbit Liver Cancer Model: An Initial Study

Aim To enhance the effect of TAE (transhepatic arterial embolization,TAE) in treating liver cancer, some adjunctive therapies using radioisotopicagents have been investigated. The present study was carried out to establishanimal model of liver cancer with four methods and choosing the steady oneas the subjects. And investigate the anticancer effect, preliminarymechanisms and their feasibility in clinic of four ¹⁸⁸Re-labeled TDDderivative.Methods New-Zealand albino rabbit liver models were established by fourmeans: inoculation of suspension cells in liver guided by ultrasound;inoculation of several little tissue pieces in liver; inoculation ofcomparatively large tissue pieces in liver; inoculation of single tissue piecewith fixed quantity in liver. After executing the rabbit model, the shortdiameter of tumors were measured and the size and consistency of tumorswere compared, inoculation of single tissue piece with fixed quantity in liver was considered as the better mean to establish liver cancer model. ¹⁸⁸ ReN-NEPTDD/lipiodol, ¹⁸⁸ReN-NEMPTDD/lipiodol, ¹⁸⁸ Re N-NEMMPTDD/lipiodol, ¹⁸⁸ReO-NEPTDD/lipiodol were perfused transhepatically in TAEtherapy. ECT scans were carried out after TAE. Region of interest(ROI)procedure was used to measure the size of tumors and the radioactivity wascounted at different time points. Time-activity(T-A) curve was drawn,nonlinear regress was used to evaluate ROI change of tumors and effectivehalf-life of the radioactive compounds in the tumors. After executing therabbit model, radioactivity of each organ and tissue in unit weight wererecorded byγcounter.Results Through inoculating single tissue piece with fixed quantity in liver,which was proved to be the ideal method of producing rabbit liver cancermodel, we found there were no remarkable metastases of tumor cell in liverand abdominal cavity, tumor size was uniform, with the smallest diameterdecibel of 5.6mm and coefficient variation of o.1.The effective half-life of thefour radioactive compounds ¹⁸⁸ Re N-NEPTDD/lipiodol, ¹⁸⁸ ReN-NEMPTDD/lipiodol, ¹⁸⁸ReN-NEMMPTDD/lipiodol, ¹⁸⁸ReO-NEPTDD/lipiodol, which were perfused transhepatically in TAE therapy in the tumors,were 4.40±0.56h,12.14±1.85h,7.85±1.01h,6.80±0.82h respectively; 24htumor/liver ratio were 0.56, 3.07, 4.12, 8.38 respectively; 24h lung/bloodratio were 0.93, 10.16, 1.25, 0.79 respectively. ECT scans showed that therewere marked radioactive disposition in bladder and colon at different timepoints in each group of radioactive compounds. There were marketradioactive disposition in lung at different time points in¹⁸⁸ReN-NEMPTDD//lipiodol group, there were less radioactive disposition in lung in other groups.Conclusion The study revealed that ¹⁸⁸ReO-NEPTDD/lipiodol has badstagnation in liver tumor, so it is unsuitable for TAE in liver cancer therapy.¹⁸⁸ReN-NEMPTDD/lipiodol has long-time stagnation in liver tumor, but haslong-time and more quantity stagnation in lung also.The effective half-life of¹⁸⁸ReN-NEMMPTDD/ lipiodol is similar to the effective half-life of¹⁸⁸Re-TDD/lipiodol in literature reports, ¹⁸⁸ReN-NEMMPTDD/ lipiodolgroup has high 24h liver/tumor ratio and has less stagnation in lung.