Targeting of VX2 rabbit liver tumor by selective delivery of 3-bromopyruvate

A biodistribution and survival study

Mustafa Vali, Josephina A. Vossen, Manon Buijs, James M. Engles, Eleni A Liapi, Veronica Prieto Ventura, Afsheen Khwaja, Obele Acha-Ngwodo, Shanmugasundara Ganapathy, Labiq Syed, Richard L. Wahl, Jean Francois H Geschwind

Research output: Contribution to journalArticle

Abstract

The aim of this study was to determine the biodistribution and tumor targeting ability of 14C-labeled 3-bromopyruvate ([ 14C]3-BrPA) after i.a. and i.v. delivery in the VX2 rabbit model. In addition, we evaluated the effects of [14C]3-BrPA on tumor and healthy tissue glucose metabolism by determining 18F-deoxy-glucose (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 [ 14C]3-BrPA i.a., 1.75 mM [14C]3-BrPA i.v., 20 mM [ 14C]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 [14C]3-BrPA in 25 ml of PBS (n = 22) with controls (n = 10). After i.a. infusion, tumor uptake of [14C]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 [14C]3-BrPA was 0.03 ± 0.01% ID/g. After i.a. administration of [14C]3-BrPA, tumor uptake of FDG was 26 times lower than in controls. After i.v. administration of [14C]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.

Original languageEnglish (US)
Pages (from-to)32-37
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume327
Issue number1
DOIs
StatePublished - Oct 2008

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Rabbits
Liver
Neoplasms
Phosphates
bromopyruvate
Glucose
Survival Analysis

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

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Targeting of VX2 rabbit liver tumor by selective delivery of 3-bromopyruvate : A biodistribution and survival study. / Vali, Mustafa; Vossen, Josephina A.; Buijs, Manon; Engles, James M.; Liapi, Eleni A; Ventura, Veronica Prieto; Khwaja, Afsheen; Acha-Ngwodo, Obele; Ganapathy, Shanmugasundara; Syed, Labiq; Wahl, Richard L.; Geschwind, Jean Francois H.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 327, No. 1, 10.2008, p. 32-37.

Research output: Contribution to journalArticle

Vali, M, Vossen, JA, Buijs, M, Engles, JM, Liapi, EA, Ventura, VP, Khwaja, A, Acha-Ngwodo, O, Ganapathy, S, Syed, L, Wahl, RL & Geschwind, JFH 2008, 'Targeting of VX2 rabbit liver tumor by selective delivery of 3-bromopyruvate: A biodistribution and survival study', Journal of Pharmacology and Experimental Therapeutics, vol. 327, no. 1, pp. 32-37. https://doi.org/10.1124/jpet.108.141093
Vali, Mustafa ; Vossen, Josephina A. ; Buijs, Manon ; Engles, James M. ; Liapi, Eleni A ; Ventura, Veronica Prieto ; Khwaja, Afsheen ; Acha-Ngwodo, Obele ; Ganapathy, Shanmugasundara ; Syed, Labiq ; Wahl, Richard L. ; Geschwind, Jean Francois H. / Targeting of VX2 rabbit liver tumor by selective delivery of 3-bromopyruvate : A biodistribution and survival study. In: Journal of Pharmacology and Experimental Therapeutics. 2008 ; Vol. 327, No. 1. pp. 32-37.
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AU - Engles, James M.

AU - Liapi, Eleni A

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AU - Khwaja, Afsheen

AU - Acha-Ngwodo, Obele

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N2 - The aim of this study was to determine the biodistribution and tumor targeting ability of 14C-labeled 3-bromopyruvate ([ 14C]3-BrPA) after i.a. and i.v. delivery in the VX2 rabbit model. In addition, we evaluated the effects of [14C]3-BrPA on tumor and healthy tissue glucose metabolism by determining 18F-deoxy-glucose (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 [ 14C]3-BrPA i.a., 1.75 mM [14C]3-BrPA i.v., 20 mM [ 14C]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 [14C]3-BrPA in 25 ml of PBS (n = 22) with controls (n = 10). After i.a. infusion, tumor uptake of [14C]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 [14C]3-BrPA was 0.03 ± 0.01% ID/g. After i.a. administration of [14C]3-BrPA, tumor uptake of FDG was 26 times lower than in controls. After i.v. administration of [14C]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.

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