Radio-frequency ablation increases intratumoral liposomal doxorubicin accumulation in a rat breast tumor model.
OBJECTIVE
To determine whether intratumoral accumulation of liposomal doxorubicin or free unencapsulated doxorubicin is increased when combined with radio-frequency (RF) ablation.


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.


CONCLUSIONS
RF ablation augments the delivery of systemic antineoplastic agents such as liposomal doxorubicin.
Dept of Radiology, Beth Israel Deaconess Med Ctr, Harvard Med School, 330 Brookline Ave, Boston, MA 02215, USA.
Wayne L
WL
Monsky
Jonathan B
JB
Kruskal
Anatoly N
AN
Lukyanov
Geoffrey D
GD
Girnun
Muneeb
M
Ahmed
G Scott
GS
Gazelle
Juan Carlos
JC
Huertas
Keith E
KE
Stuart
Vladimir P
VP
Torchilin
S Nahum
SN
Goldberg
D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D001345:Autoradiography; D017115:Catheter Ablation; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D007275:Injections, Intravenous; D008081:Liposomes; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D000970:Antineoplastic Agents; D008081:Liposomes; D004317:Doxorubicin