A nanoengineered embolic agent for precise radiofrequency ablation.
The purpose of the work is to investigate whether the electromagnetic properties of multi-walled carbon nanotubes (MWCNT) in the presence of radiofrequency (RF) energy is (1) safe, and (2) improves the precision of the therapeutic efficiency of the RF-ablation (RFA) procedure. An in vitro phantom was created for evaluating temperature near RF treated nanotubes. For the in vivo study, three baboons and six pigs were submitted for RFA procedure in superior/inferior kidney poles embolized with a non-adherent, lipophilic embolic agent (marsembol) with or without MWCNT. Tissue damage in the surrounding kill zone was assayed through caspase-3 activation. The in vitro results showed marked heat increase only in the region of the nanotubes. In vivo, necrosis/ischemic damage resulted from RFA therapy alone, RFA plus marsembol only. In marsembol + MWCNT condition, dramatic disruption of cell membranes and sub-cellular organelles was found whereas the nuclear membranes and basal cell membranes remained largely intact. The marsembol vaporized under RFA and tissue fluid filled the space. This caused the MWCNT to cluster within the new aqueous environment. RFA plus marsembol + MWCNT created a well-defined demarcation between healthy and apoptotic cells as evidenced by a marked reduction of caspase-3 expression. By contrast, there was a much less defined ablation zone in the absence of MWCNT. In conclusion, the combination of RFA plus marsembol + MWCNT embolization delineated the kill zone in vitro and in vivo. We demonstrate that MWCNTs remain in the ablation region thus minimizing their migration to the systemic circulation.
Experimental Interventional Imaging Laboratory, European Center for Medical Imaging Research, School of Medicine, Aix-Marseille University, Marseilles, France.
Pierre Henri
PH
Rolland
Joel L
JL
Berry
Guillaume
G
Louis
Lionel
L
Velly
Vincent
V
Vidal
Pauline
P
Brige
Vinuta
V
Mayakonda
David L
DL
Carroll
D000818:Animals; D002122:Calcium Chloride / Q000737:chemistry; D017115:Catheter Ablation / Q000379:methods*; D016923:Cell Death; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D004621:Embolization, Therapeutic / Q000379:methods*; D004998:Ethiodized Oil / Q000737:chemistry; D005780:Gelatin / Q000737:chemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D037742:Nanotubes, Carbon / Q000737:chemistry; D010215:Papio; D012118:Resorcinols / Q000737:chemistry; D013552:Swine
D004337:Drug Carriers; D037742:Nanotubes, Carbon; D012118:Resorcinols; D004998:Ethiodized Oil; D005780:Gelatin; D002122:Calcium Chloride; C031389:resorcinol