title: Combined radiofrequency ablation and adjuvant liposomal chemotherapy: effect of chemotherapeutic agent, nanoparticle size, and circulation time.
abstract: OBJECTIVE
  To evaluate the effects of liposomal chemotherapeutic agent, nanoparticle size, and liposome circulation time on tissue coagulation and intratumoral drug uptake when radiofrequency (RF) ablation is combined with adjuvant intravenous liposomal chemotherapy in an animal breast tumor model.
  
  
  METHODS
  Ninety-one R3230 mammary adenocarcinoma nodules were implanted in 48 Fischer rats. First, standardized RF ablation was combined with intravenous liposomal doxorubicin, cisplatin, or 5-fluorouracil (35 tumors each). Second, three different-sized doxorubicin-containing nanoparticle preparations were combined with standardized RF ablation. Last, two doxorubicin-containing liposome preparations with different blood elimination half-lives were combined with RF ablation. Coagulation diameter and interstitial doxorubicin concentration were measured 48 hours after treatment and compared with use of statistical analysis.
  
  
  RESULTS
  All combinations of RF with liposomal chemotherapy caused significantly greater tumor necrosis than RF alone (P<.05). Significantly increased necrosis was observed with intravenous liposomal RF/doxorubicin and RF/cisplatin compared with intravenous liposomal RF/5-fluorouracil (P<.01). Greater coagulation was observed with RF combined with 100-nm nanoparticles compared with 20-nm or 250-nm nanoparticles (P=.01 and P=.04, respectively). Additionally, greater intratumoral doxorubicin uptake was observed in the group treated with 20-nm nanoparticles compared with those treated with other sizes of nanoparticles (P<.05). RF plus liposomal doxorubicin produced greater coagulation and intratumoral doxorubicin uptake than RF plus 1,2-dipalmitoyl-sn-glycero-3-phosphatidic acid (P<.05).
  
  
  CONCLUSIONS
  When combined with RF ablation, modification of adjuvant intravenous liposomal chemotherapy, including nanoparticle size, circulation time, and chemotherapeutic agent, can influence intratumoral drug accumulation and tissue coagulation.
authors.affiliation: Laboratory for Minimally Invasive Tumor Therapy, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Muneeb
authors.initials: M
authors.lastname: Ahmed
authors.forename: Anatoly N
authors.initials: AN
authors.lastname: Lukyanov
authors.forename: Vladimir
authors.initials: V
authors.lastname: Torchilin
authors.forename: Herve
authors.initials: H
authors.lastname: Tournier
authors.forename: Anatoly N
authors.initials: AN
authors.lastname: Schneider
authors.forename: S Nahum
authors.initials: SN
authors.lastname: Goldberg
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D017115:Catheter Ablation; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005472:Fluorouracil / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D049329:Nanostructures; D009336:Necrosis; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil