03381nas a2200397 4500008004100000022001400041245011600055210006900171260001300240300001000253490000800263520219300271653001902464653001202483653002602495653002002521653002202541653001602563653001102579653002802590653001402618653003602632653000902668653002202677100002102699700002502720700002502745700002402770700001802794700001902812700002602831700002102857700002702878700002002905856005802925 2002 eng d a0033-841900aRadio-frequency ablation increases intratumoral liposomal doxorubicin accumulation in a rat breast tumor model.0 aRadiofrequency ablation increases intratumoral liposomal doxorub c2002 Sep a823-90 v2243 a

PURPOSE: To determine whether intratumoral accumulation of liposomal doxorubicin or free unencapsulated doxorubicin is increased when combined with radio-frequency (RF) ablation.

MATERIALS AND METHODS: Two 1.2-1.5-cm R3230 mammary adenocarcinomas were grown within the mammary fat pads of 19 female Fischer rats. One tumor of each pair was treated with RF ablation (tip temperature, 70 degrees C +/- 2 [SD]; 120 mA +/- 75) for 5 minutes, whereas the other tumor was a control. Intravenous liposomal doxorubicin (1 mg in 500 micro L, n = 6) or intravenous free unencapsulated doxorubicin (n = 7) was administered immediately following RF ablation. Doxorubicin was extracted in acid alcohol from tumors 24 hours following RF ablation, and fluorescent spectrophotometry was used to quantify extracted doxorubicin. Comparisons of intratumoral doxorubicin accumulation in tumors treated with RF ablation and in untreated tumors were analyzed with parametric (paired Student t test) and nonparametric (Wilcoxon rank sum test) statistics. Findings at autoradiography with densitometry (six additional tumors) demonstrated the spatial distribution of the intratumoral accumulation of liposomal doxorubicin.

RESULTS: When RF ablation preceded administration of liposomal doxorubicin, mean intratumoral doxorubicin concentration was 5.6 micro g/g +/- 2.1 (range, 1.9-7.7 micro g/g), whereas 1.0 micro g/g +/- 0.4 (range, 0.5-1.5 micro g/g) was present in control tumors not treated with RF ablation (P <.05). Thus, there was a mean 7.1-fold +/- 4.9 increase in intratumoral doxorubicin accumulation following RF ablation (range, 2.1-14.5-fold) compared with the amount without RF pretreatment (P <.05). Increased intratumoral accumulation was not seen in animals receiving free doxorubicin with (mean, 0.4 micro g/g +/- 0.1) or without (mean, 0.8 micro g/g +/- 0.4) RF pretreatment (P =.07). Autoradiographic findings demonstrated accumulation of liposomal doxorubicin in a peripheral rim of tumor adjacent to the zone of coagulation.

CONCLUSION: RF ablation augments the delivery of systemic antineoplastic agents such as liposomal doxorubicin.

10aAdenocarcinoma10aAnimals10aAntineoplastic Agents10aAutoradiography10aCatheter Ablation10aDoxorubicin10aFemale10aInjections, Intravenous10aLiposomes10aMammary Neoplasms, Experimental10aRats10aRats, Inbred F3441 aMonsky, Wayne, L1 aKruskal, Jonathan, B1 aLukyanov, Anatoly, N1 aGirnun, Geoffrey, D1 aAhmed, Muneeb1 aGazelle, Scott1 aHuertas, Juan, Carlos1 aStuart, Keith, E1 aTorchilin, Vladimir, P1 aGoldberg, Nahum uhttp://www.microfluidicsciences.com/drupal/?q=node/27