title: Targeting of VX2 rabbit liver tumor by selective delivery of 3-bromopyruvate: a biodistribution and survival study.
abstract: The aim of this study was to determine the biodistribution and tumor targeting ability of (14)C-labeled 3-bromopyruvate ([(14)C]3-BrPA) after i.a. and i.v. delivery in the VX2 rabbit model. In addition, we evaluated the effects of [(14)C]3-BrPA on tumor and healthy tissue glucose metabolism by determining (18)F-deoxyglucose (FDG) uptake. Last, we determined the survival benefit of i.a. administered 3-BrPA. In total, 60 rabbits with VX2 liver tumor received either 1.75 mM [(14)C]3-BrPA i.a., 1.75 mM [(14)C]3-BrPA i.v., 20 mM [(14)C]3-BrPA i.v., or 25 ml of phosphate-buffered saline (PBS). All rabbits (with the exception of the 20 mM i.v. group) received FDG 1 h before sacrifice. Next, we compared survival of animals treated with i.a. administered 1.75 mM [(14)C]3-BrPA in 25 ml of PBS (n = 22) with controls (n = 10). After i.a. infusion, tumor uptake of [(14)C]3-BrPA was 1.8 +/- 0.2% percentage of injected dose per gram of tissue (%ID/g), whereas other tissues showed minimal uptake. After i.v. infusion (1.75 mM), tumor uptake of [(14)C]3-BrPA was 0.03 +/- 0.01% ID/g. After i.a. administration of [(14)C]3-BrPA, tumor uptake of FDG was 26 times lower than in controls. After i.v. administration of [(14)C]3-BrPA, there was no significant difference in tumor FDG uptake. Survival analysis showed that rabbits treated with 1.75 mM 3-BrPA survived longer (55 days) than controls (18.6 days). Intra-arterially delivered 3-BrPA has a favorable biodistribution profile, combining a high tumor uptake resulting in blockage of FDG uptake with no effects on healthy tissue. The local control of the liver tumor by 3-BrPA resulted in a significant survival benefit.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Sciences, Division of Vascular and Interventional Radiology, Johns Hopkins Hospital, Baltimore, MD 21287, USA.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Vali
authors.forename: Josephina A
authors.initials: JA
authors.lastname: Vossen
authors.forename: Manon
authors.initials: M
authors.lastname: Buijs
authors.forename: James M
authors.initials: JM
authors.lastname: Engles
authors.forename: Eleni
authors.initials: E
authors.lastname: Liapi
authors.forename: Veronica Prieto
authors.initials: VP
authors.lastname: Ventura
authors.forename: Afsheen
authors.initials: A
authors.lastname: Khwaja
authors.forename: Obele
authors.initials: O
authors.lastname: Acha-Ngwodo
authors.forename: Shanmugasundaram
authors.initials: S
authors.lastname: Ganapathy-Kanniappan
authors.forename: Ganapathy
authors.initials: G
authors.lastname: Shanmugasundaram
authors.forename: Labiq
authors.initials: L
authors.lastname: Syed
authors.forename: Richard L
authors.initials: RL
authors.lastname: Wahl
authors.forename: Jean-Francois H
authors.initials: JF
authors.lastname: Geschwind
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes; D019788:Fluorodeoxyglucose F18; D007261:Infusions, Intra-Arterial; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000401:mortality; D011773:Pyruvates / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011817:Rabbits; D014018:Tissue Distribution
chemical_list: D002250:Carbon Radioisotopes; D011773:Pyruvates; D019788:Fluorodeoxyglucose F18; C017092:bromopyruvate