| As a minimally invasive treatment, radiofrequency ablation(RFA) hasbeen widely used to treat a variety of solid tumors and has led to promisingeffects. However, its application is largely limited by tumor size andlocation. The out margin of larger tumor(more than 3 cm diameter) may notbe ablated since temperature in the periphery is not high enough to destroycancer cell. In recent years, temperature sensitive liposomes(TSLs) aredrawing more and more attention. But, because of the limitation ofhyperthermia devices and technology, TSLs have not been successfullyused in clinic. We postulate if RFA is combined with TSLs, drugs candeposit around the ablation zone and this will increase the region of tissuethat can be treated beyond the area by RFA alone. In addition, combiningwith TSLs, tumor cells adjacent to critical organs can be killed at arelatively lower temperature without injuring those organs. Vinorelbine is akind of half-synthetic vinca alcaloid and its antitumor effects especially inadvanced breast cancer and non-small cell lung cancer has been proven.Vinorelbine is one of the most common antitumor chemotherapy drugsworldwide. Vinorelbine long-circulating temperature sensitive liposome isa new type of temperature sensitive liposome. The objective of this study isto explore the feasibility and antitumor efficacy of temperature sensitiveliposome and RFA on VX2 muscle tumor in rabbits.The rabbit VX2 muscle tumor model was established by two methods:ultrasound-guided percutaneous tissue block inoculation and tissue massincision embedding. We compared the tumor growth rate and the procedure. Tumors were evaluated using ultrasound at 7, 14, 21 and 26 days after theinoculation. 26th day after inoculation, the rabbits were then sacrificed andtumors were stipped, measured with digimatic caliper and sections weresent for pathologic examination. We compared the size of tumors onpathologic examination and on ultrasonography on 26th day afterinoculation. The results showed that the success rate of implanted tumor byultrasound-guidance and via incision route was 100% and 80% respectively.The time of inoculation was (93.7±7.4)s and (251.8±17.8)s respectively.Significant differences of the two values were found between theultrasound-guidance and via incision route(P＜0.05). The tumors of both ofthe groups are solitary and uniform. Tumors growed well withoutdegeneration necrosis during 7 to 14 days after the inoculation. On 21th daythere were few necrosis areas in some tumors. With the extension of time,the necrosis parts of tumors increased gradually. And the results alsoindicated that interventional therapy of tumors should be performed 2 to 3weeks after the inculation. Compared with the tumor volumes byultrasonography measurement with anatomical measurement, the resultssuggested that they had better consistency. It showed the accuracy ofmonitoring tumor by ultrasonography.Animal tumor models were established by ultrasound-guided methodabove. VX2 muscle tumor models were randomly assinged into fourtreatment groups: normal saline(NS), free vinorelbine(VRB), vinorelbinelong-circulating liposomes(VLCL) or vinorelbine low-temperaturesensitive liposomes(VLTSL). After the intravenous injection of drugs, oneof the two tumors in each rabbit received RF exposure(1W, 30min),non-exposed tumors served as internal contrast. The treatments wererepeated on days 1, 4, and 7 respectively. Ultrasonography was performedbefore and after the treatments. The tumor volume and inhibition rate(IR)of tumor growth were calculated and compared between the two methods.All experimental animals were executed on the 1st day after treatment finished and followed by pathologic examination of the tumors. Compareddecreased(P＜0.05). The IR of this group was the highest(48%). Whenboth sides of the tumors in normal saline group, free vinorelbine group andvinorelbine long-circulating liposomes group were compared, thedifferences were not statistically significant(P>0.05). These showed thatlow-power radiofrequency alone didn't have an obvious inhibition on tumorgrowth. The study of pathologic examination indicated that the necrosisextent was the most extensive. The results indicated that the anti-tumoreffect of TSLs combined with low-power RF was obvious.To sum up, the method of ultrasound-guided implanting tumor tissuesfor establishing rabbit VX2 muscle tumor model is simple-operating,time-saving, high success rate and growth-uniformed. It is an ideal imaginganimal model to evaluate the intervention therapy of tumor.Ultrasonography plays an important role in monitoring the rabbit VX2muscle tumors dynamically as a preferred imaging method in tumorfollow-up. Low-power radiofrequency as temperature sensitive liposomeheating method is safe and vinorelbine temperature sensitive liposomescombined with low-power radiofrequency can significantly inhibit thegrowth of VX2 muscle tumor in rabbits.
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