03546nas a2200469 4500008004100000022001400041245015800055210006900213260001300282300001200295490000800307520208900315653001202404653002602416653002202442653003002464653001602494653001102510653002702521653001402548653003602562653001302598653002902611653002502640653000902665653002202674653002602696653002602722100002002748700002402768700002502792700001802817700002102835700001902856700002602875700002102901700002002922700002802942700002202970700002502992856005903017 2002 eng d a0033-841900aPercutaneous tumor ablation: increased necrosis with combined radio-frequency ablation and intravenous liposomal doxorubicin in a rat breast tumor model.0 aPercutaneous tumor ablation increased necrosis with combined rad c2002 Mar a797-8040 v2223 a

PURPOSE: To determine whether a combination of intravenous liposomal doxorubicin and radio-frequency (RF) ablation increases tumor destruction compared with RF alone in an animal tumor model.

MATERIALS AND METHODS: R3230 mammary adenocarcinoma 1.4-1.8-cm- diameter nodules were implanted subcutaneously in 132 female Fischer rats. Initially, tumors were treated with (a) conventional, monopolar RF (mean, 250 mA +/- 25 [SD] at 70 degrees C +/- 1 for 5 minutes) ablation alone, (b) RF ablation followed by intravenous administration of 1 mg of liposomal doxorubicin, (c) RF ablation followed by intravenous administration of 1 mg of empty liposomes, (d) RF ablation and direct intratumoral administration of liposomal doxorubicin, or (e) no treatment. Subsequently, the dose (0.06-2.00 mg) of liposomal doxorubicin, the timing of administration (3 days before to 3 days after RF ablation), and the time of pathologic examination (0-72 hours after treatment) were varied.

RESULTS: Mean coagulation diameter for treated tumors follows: 6.7 mm +/- 0.6, RF ablation alone; 11.1 mm +/- 1.5, RF ablation and intravenous administration of empty liposomes (P <.05, compared with RF ablation alone); and 8.4 mm +/- 1.1, RF ablation with intratumoral administration of liposomal doxorubicin (P <.05, compared with RF ablation alone). Maximal increased mean coagulation diameter (13.1 mm +/- 1.5) was observed with a combination of liposomal doxorubicin and RF ablation (P <.001, for all comparisons). The increased coagulation for combination therapy developed over 48 hours after therapy. Coagulation diameter did not vary with the doxorubicin concentration range and was not dependent on the timing of administration of liposomal doxorubicin from 3 days before to 24 hours after RF ablation.

CONCLUSION: Intravenous administration of liposomal doxorubicin can improve RF ablation, since it increases coagulation diameter in solid tumors compared with RF ablation alone or a combination of RF ablation with administration of empty liposomes.

10aAnimals10aAntineoplastic Agents10aCatheter Ablation10aCombined Modality Therapy10aDoxorubicin10aFemale10aInfusions, Intravenous10aLiposomes10aMammary Neoplasms, Experimental10aNecrosis10aNeoplasm Transplantation10aPolyethylene Glycols10aRats10aRats, Inbred F34410aSurface-Active Agents10aTumor Cells, Cultured1 aGoldberg, Nahum1 aGirnan, Geoffrey, D1 aLukyanov, Anatoly, N1 aAhmed, Muneeb1 aMonsky, Wayne, L1 aGazelle, Scott1 aHuertas, Juan, Carlos1 aStuart, Keith, E1 aJacobs, Timothy1 aTorchillin, Vladimir, P1 aHalpern, Elkan, F1 aKruskal, Jonathan, B uhttps://www.microfluidicsciences.com/drupal/?q=node/2903382nas a2200397 4500008004100000022001400041245011600055210006900171260001300240300001000253490000800263520219300271653001902464653001202483653002602495653002002521653002202541653001602563653001102579653002802590653001402618653003602632653000902668653002202677100002102699700002502720700002502745700002402770700001802794700001902812700002602831700002102857700002702878700002002905856005902925 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 uhttps://www.microfluidicsciences.com/drupal/?q=node/27