Targeting of VX2 rabbit liver tumor by selective delivery of 3-bromopyruvate: a biodistribution and survival study.
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.
Vali
Mustafa
M
Russell H. Morgan Department of Radiology and Radiological Sciences, Division of Vascular and Interventional Radiology, Johns Hopkins Hospital, Baltimore, MD 21287, USA.
Vossen
Josephina A
JA
Buijs
Manon
M
Engles
James M
JM
Liapi
Eleni
E
Ventura
Veronica Prieto
VP
Khwaja
Afsheen
A
Acha-Ngwodo
Obele
O
Ganapathy-Kanniappan
Shanmugasundaram
S
Shanmugasundaram
Ganapathy
G
Syed
Labiq
L
Wahl
Richard L
RL
Geschwind
Jean-Francois H
JF
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
D002250:Carbon Radioisotopes; D011773:Pyruvates; D019788:Fluorodeoxyglucose F18; C017092:bromopyruvate