title: Nonthermal Ablation by Using Intravascular Oxygen Radical Generation with WST11: Dynamic Tissue Effects and Implications for Focal Therapy.
abstract: Purpose To examine the hypothesis that vascular-targeted photodynamic therapy (VTP) with WST11 and clinically relevant parameters can be used to ablate target tissues in a non-tumor-bearing large-animal model while selectively sparing blood vessels and collagen. Materials and Methods By using an institutional animal care and use committee-approved protocol, 68 ablations were performed in the kidneys (cortex and medulla) and livers of 27 adult pigs. Posttreatment evaluation was conducted with contrast material-enhanced computed tomography in the live animals at 24 hours. Immunohistochemistry was evaluated and histologic examination with hematoxylin-eosin staining was performed at 4 hours, 24 hours, and 7 days. Intravenous infusion of WST11 (4 mg per kilogram of body weight) was followed by using near-infrared illumination (753 nm for 20 minutes) through optical fibers prepositioned in target tissues by using a fixed template. Treated areas were scanned, measured, and statistically analyzed by using the Student t test and two-way analysis of variance. Results Focal WST11 VTP treatment in the liver and kidney by using a single optical fiber resulted in well-demarcated cylindrical zones of nonthermal necrosis concentrically oriented around the light-emitting diffuser, with no intervening viable parenchymal cells. The radius of ablated tissue increased from approximately 5 mm at 150 mW to approximately 7 mm at 415 mW (P < .01). Illumination through fiber triads at 1-cm separation resulted in confluent homogeneous necrosis. Patterns of acute injury within 24 hours were consistent with microcirculatory flow arrest and collagen preservation (demonstrated with trichrome staining). In the peripheral ablation zone, blood vessels at least 40 μm in diameter were selectively preserved and remained functional at 7 days. Ablated tissues exhibited progressive fibrosis and chronic inflammatory cell infiltrates. No histologic changes consistent with thermal injury were observed in blood vessels or collagen. The renal hilum and collecting system did not show treatment effect, despite treatment proximity. Conclusion WST11 VTP induces nonthermal tissue ablation in target tissue while preserving critical organ structures and bystander blood vessels within solid organs. (©) RSNA, 2016 Online supplemental material is available for this article.
authors.affiliation: From the Urology Service, Department of Surgery (S.Y.K., D.G., P.T.S., J.C.), Tri-Institutional Laboratory of Comparative Pathology, Rockefeller University, Weill Cornell Medical College (S.M.), Radiochemistry and Imaging Sciences Service (G.S.), and Interventional Radiology Service (J.C.D., S.B.S.), Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065; Department of Urology, University of Pittsburgh Medical Center, Pittsburgh, Pa (T.V.T.); and Department of Plant Sciences, Weizmann Institute of Science, Rehovot, Israel (A.S.).
authors.forename: Simon Y
authors.initials: SY
authors.lastname: Kimm
authors.affiliation: From the Urology Service, Department of Surgery (S.Y.K., D.G., P.T.S., J.C.), Tri-Institutional Laboratory of Comparative Pathology, Rockefeller University, Weill Cornell Medical College (S.M.), Radiochemistry and Imaging Sciences Service (G.S.), and Interventional Radiology Service (J.C.D., S.B.S.), Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065; Department of Urology, University of Pittsburgh Medical Center, Pittsburgh, Pa (T.V.T.); and Department of Plant Sciences, Weizmann Institute of Science, Rehovot, Israel (A.S.).
authors.forename: Tatum V
authors.initials: TV
authors.lastname: Tarin
authors.affiliation: From the Urology Service, Department of Surgery (S.Y.K., D.G., P.T.S., J.C.), Tri-Institutional Laboratory of Comparative Pathology, Rockefeller University, Weill Cornell Medical College (S.M.), Radiochemistry and Imaging Sciences Service (G.S.), and Interventional Radiology Service (J.C.D., S.B.S.), Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065; Department of Urology, University of Pittsburgh Medical Center, Pittsburgh, Pa (T.V.T.); and Department of Plant Sciences, Weizmann Institute of Science, Rehovot, Israel (A.S.).
authors.forename: Sébastien
authors.initials: S
authors.lastname: Monette
authors.affiliation: From the Urology Service, Department of Surgery (S.Y.K., D.G., P.T.S., J.C.), Tri-Institutional Laboratory of Comparative Pathology, Rockefeller University, Weill Cornell Medical College (S.M.), Radiochemistry and Imaging Sciences Service (G.S.), and Interventional Radiology Service (J.C.D., S.B.S.), Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065; Department of Urology, University of Pittsburgh Medical Center, Pittsburgh, Pa (T.V.T.); and Department of Plant Sciences, Weizmann Institute of Science, Rehovot, Israel (A.S.).
authors.forename: Govindarajan
authors.initials: G
authors.lastname: Srimathveeravalli
authors.affiliation: From the Urology Service, Department of Surgery (S.Y.K., D.G., P.T.S., J.C.), Tri-Institutional Laboratory of Comparative Pathology, Rockefeller University, Weill Cornell Medical College (S.M.), Radiochemistry and Imaging Sciences Service (G.S.), and Interventional Radiology Service (J.C.D., S.B.S.), Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065; Department of Urology, University of Pittsburgh Medical Center, Pittsburgh, Pa (T.V.T.); and Department of Plant Sciences, Weizmann Institute of Science, Rehovot, Israel (A.S.).
authors.forename: Daniel
authors.initials: D
authors.lastname: Gerber
authors.affiliation: From the Urology Service, Department of Surgery (S.Y.K., D.G., P.T.S., J.C.), Tri-Institutional Laboratory of Comparative Pathology, Rockefeller University, Weill Cornell Medical College (S.M.), Radiochemistry and Imaging Sciences Service (G.S.), and Interventional Radiology Service (J.C.D., S.B.S.), Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065; Department of Urology, University of Pittsburgh Medical Center, Pittsburgh, Pa (T.V.T.); and Department of Plant Sciences, Weizmann Institute of Science, Rehovot, Israel (A.S.).
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Durack
authors.affiliation: From the Urology Service, Department of Surgery (S.Y.K., D.G., P.T.S., J.C.), Tri-Institutional Laboratory of Comparative Pathology, Rockefeller University, Weill Cornell Medical College (S.M.), Radiochemistry and Imaging Sciences Service (G.S.), and Interventional Radiology Service (J.C.D., S.B.S.), Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065; Department of Urology, University of Pittsburgh Medical Center, Pittsburgh, Pa (T.V.T.); and Department of Plant Sciences, Weizmann Institute of Science, Rehovot, Israel (A.S.).
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Solomon
authors.affiliation: From the Urology Service, Department of Surgery (S.Y.K., D.G., P.T.S., J.C.), Tri-Institutional Laboratory of Comparative Pathology, Rockefeller University, Weill Cornell Medical College (S.M.), Radiochemistry and Imaging Sciences Service (G.S.), and Interventional Radiology Service (J.C.D., S.B.S.), Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065; Department of Urology, University of Pittsburgh Medical Center, Pittsburgh, Pa (T.V.T.); and Department of Plant Sciences, Weizmann Institute of Science, Rehovot, Israel (A.S.).
authors.forename: Peter T
authors.initials: PT
authors.lastname: Scardino
authors.affiliation: From the Urology Service, Department of Surgery (S.Y.K., D.G., P.T.S., J.C.), Tri-Institutional Laboratory of Comparative Pathology, Rockefeller University, Weill Cornell Medical College (S.M.), Radiochemistry and Imaging Sciences Service (G.S.), and Interventional Radiology Service (J.C.D., S.B.S.), Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065; Department of Urology, University of Pittsburgh Medical Center, Pittsburgh, Pa (T.V.T.); and Department of Plant Sciences, Weizmann Institute of Science, Rehovot, Israel (A.S.).
authors.forename: Avigdor
authors.initials: A
authors.lastname: Scherz
authors.affiliation: From the Urology Service, Department of Surgery (S.Y.K., D.G., P.T.S., J.C.), Tri-Institutional Laboratory of Comparative Pathology, Rockefeller University, Weill Cornell Medical College (S.M.), Radiochemistry and Imaging Sciences Service (G.S.), and Interventional Radiology Service (J.C.D., S.B.S.), Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065; Department of Urology, University of Pittsburgh Medical Center, Pittsburgh, Pa (T.V.T.); and Department of Plant Sciences, Weizmann Institute of Science, Rehovot, Israel (A.S.).
authors.forename: Jonathan
authors.initials: J
authors.lastname: Coleman
mesh_terms: D000818:Animals; D001429:Bacteriochlorophylls / Q000494:pharmacology*; D003287:Contrast Media; D005260:Female; D007150:Immunohistochemistry; D007668:Kidney / Q000000981:diagnostic imaging / Q000187:drug effects*; D008099:Liver / Q000000981:diagnostic imaging / Q000187:drug effects*; D023421:Models, Animal; D009336:Necrosis; D055100:Optical Fibers; D010778:Photochemotherapy / Q000379:methods*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013552:Swine; D014057:Tomography, X-Ray Computed
chemical_list: D001429:Bacteriochlorophylls; D003287:Contrast Media; D017382:Reactive Oxygen Species; C503696:padeliporfin