Assessment of tumoricidal efficacy and response to treatment with 18F-FDG PET/CT after intraarterial infusion with the antiglycolytic agent 3-bromopyruvate in the VX2 model of liver tumor

Eleni A Liapi, Jean Francois H Geschwind, Mustafa Vali, Afsheen A. Khwaja, Veronica Prieto-Ventura, Manon Buijs, Josephina A. Vossen, Shanmugasundara Ganapathy, Richard L. Wahl

Research output: Contribution to journalArticle

Abstract

The purpose of this study was to determine the effects of 3-bromopyruvate (3-BrPA) on tumor glucose metabolism as imaged with 18F-FDG PET/CT at multiple time points after treatment and compare them with those after intraarterial control injections of saline. Methods: Twenty-three New Zealand White rabbits implanted intrahepatically with VX2 tumors were assigned to 1 of 2 groups: 14 rabbits were assigned to the treatment group (TG) and 9 to the saline control group (SG). All animals were infused with 25 mL of either 1.75 mM 3-BrPA or saline over 1 h via a 2-French catheter, which was secured in the hepatic artery. For PET/CT, the animals were injected with 37 MBq of 18F-FDG at 1 d before treatment and 2 h, 24 h, and 1 wk after treatment. Tumor size, tumor and liver maximal standardized uptake value (SUVmax), and tumor-to-background ratios were calculated for all studies. Seven TG and 5 SG animals were sacrificed at 1 wk after treatment for histopathologic analysis. Results: Intense 18F-FDG uptake was seen in untreated tumors. A significant reduction in tumor SUVmax was noted in TG animals, when compared with SG animals, at 1 wk after treatment (P = 0.006). The tumor-to-liver background ratio in the TG animals, compared with the SG animals, was significantly reduced as early as 24 h after treatment (P = 0.01) and remained reduced at 1 wk (P = 0.003). Tumor SUVmax increased from the baseline levels at 7 d in controls (P = 0.05). The histopathologic analysis of explanted livers revealed increased tumor necrosis in all TG samples. There was a significant inverse correlation (r2 = 0.538, P = 0.005) between the percentage of tumor necrosis on histopathology and tumor SUVmax on 18F-FDG PET at 7 d after treatment with 3-BrPA. Conclusion: Intraarterial injection of 3-BrPA resulted in markedly decreased 18F-FDG uptake as imaged by PET/CT and increased tumor necrosis on histopathology at 1 wk after treatment in the VX2 rabbit liver tumor. PET/CT appears to be a useful means to follow antiglycolytic therapy with 3-BrPA.

Original languageEnglish (US)
Pages (from-to)225-230
Number of pages6
JournalJournal of Nuclear Medicine
Volume52
Issue number2
DOIs
StatePublished - Feb 1 2011

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Intra Arterial Infusions
Fluorodeoxyglucose F18
Liver
Neoplasms
Therapeutics
Intra-Arterial Injections
Control Groups
Necrosis
Rabbits
bromopyruvate
Hepatic Artery

Keywords

  • 3-bromopyruvate
  • Hepatology
  • Interventional
  • Liver cancer
  • PET/CT
  • VX2

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Assessment of tumoricidal efficacy and response to treatment with 18F-FDG PET/CT after intraarterial infusion with the antiglycolytic agent 3-bromopyruvate in the VX2 model of liver tumor. / Liapi, Eleni A; Geschwind, Jean Francois H; Vali, Mustafa; Khwaja, Afsheen A.; Prieto-Ventura, Veronica; Buijs, Manon; Vossen, Josephina A.; Ganapathy, Shanmugasundara; Wahl, Richard L.

In: Journal of Nuclear Medicine, Vol. 52, No. 2, 01.02.2011, p. 225-230.

Research output: Contribution to journalArticle

Liapi, Eleni A ; Geschwind, Jean Francois H ; Vali, Mustafa ; Khwaja, Afsheen A. ; Prieto-Ventura, Veronica ; Buijs, Manon ; Vossen, Josephina A. ; Ganapathy, Shanmugasundara ; Wahl, Richard L. / Assessment of tumoricidal efficacy and response to treatment with 18F-FDG PET/CT after intraarterial infusion with the antiglycolytic agent 3-bromopyruvate in the VX2 model of liver tumor. In: Journal of Nuclear Medicine. 2011 ; Vol. 52, No. 2. pp. 225-230.
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abstract = "The purpose of this study was to determine the effects of 3-bromopyruvate (3-BrPA) on tumor glucose metabolism as imaged with 18F-FDG PET/CT at multiple time points after treatment and compare them with those after intraarterial control injections of saline. Methods: Twenty-three New Zealand White rabbits implanted intrahepatically with VX2 tumors were assigned to 1 of 2 groups: 14 rabbits were assigned to the treatment group (TG) and 9 to the saline control group (SG). All animals were infused with 25 mL of either 1.75 mM 3-BrPA or saline over 1 h via a 2-French catheter, which was secured in the hepatic artery. For PET/CT, the animals were injected with 37 MBq of 18F-FDG at 1 d before treatment and 2 h, 24 h, and 1 wk after treatment. Tumor size, tumor and liver maximal standardized uptake value (SUVmax), and tumor-to-background ratios were calculated for all studies. Seven TG and 5 SG animals were sacrificed at 1 wk after treatment for histopathologic analysis. Results: Intense 18F-FDG uptake was seen in untreated tumors. A significant reduction in tumor SUVmax was noted in TG animals, when compared with SG animals, at 1 wk after treatment (P = 0.006). The tumor-to-liver background ratio in the TG animals, compared with the SG animals, was significantly reduced as early as 24 h after treatment (P = 0.01) and remained reduced at 1 wk (P = 0.003). Tumor SUVmax increased from the baseline levels at 7 d in controls (P = 0.05). The histopathologic analysis of explanted livers revealed increased tumor necrosis in all TG samples. There was a significant inverse correlation (r2 = 0.538, P = 0.005) between the percentage of tumor necrosis on histopathology and tumor SUVmax on 18F-FDG PET at 7 d after treatment with 3-BrPA. Conclusion: Intraarterial injection of 3-BrPA resulted in markedly decreased 18F-FDG uptake as imaged by PET/CT and increased tumor necrosis on histopathology at 1 wk after treatment in the VX2 rabbit liver tumor. PET/CT appears to be a useful means to follow antiglycolytic therapy with 3-BrPA.",
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author = "Liapi, {Eleni A} and Geschwind, {Jean Francois H} and Mustafa Vali and Khwaja, {Afsheen A.} and Veronica Prieto-Ventura and Manon Buijs and Vossen, {Josephina A.} and Shanmugasundara Ganapathy and Wahl, {Richard L.}",
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T1 - Assessment of tumoricidal efficacy and response to treatment with 18F-FDG PET/CT after intraarterial infusion with the antiglycolytic agent 3-bromopyruvate in the VX2 model of liver tumor

AU - Liapi, Eleni A

AU - Geschwind, Jean Francois H

AU - Vali, Mustafa

AU - Khwaja, Afsheen A.

AU - Prieto-Ventura, Veronica

AU - Buijs, Manon

AU - Vossen, Josephina A.

AU - Ganapathy, Shanmugasundara

AU - Wahl, Richard L.

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N2 - The purpose of this study was to determine the effects of 3-bromopyruvate (3-BrPA) on tumor glucose metabolism as imaged with 18F-FDG PET/CT at multiple time points after treatment and compare them with those after intraarterial control injections of saline. Methods: Twenty-three New Zealand White rabbits implanted intrahepatically with VX2 tumors were assigned to 1 of 2 groups: 14 rabbits were assigned to the treatment group (TG) and 9 to the saline control group (SG). All animals were infused with 25 mL of either 1.75 mM 3-BrPA or saline over 1 h via a 2-French catheter, which was secured in the hepatic artery. For PET/CT, the animals were injected with 37 MBq of 18F-FDG at 1 d before treatment and 2 h, 24 h, and 1 wk after treatment. Tumor size, tumor and liver maximal standardized uptake value (SUVmax), and tumor-to-background ratios were calculated for all studies. Seven TG and 5 SG animals were sacrificed at 1 wk after treatment for histopathologic analysis. Results: Intense 18F-FDG uptake was seen in untreated tumors. A significant reduction in tumor SUVmax was noted in TG animals, when compared with SG animals, at 1 wk after treatment (P = 0.006). The tumor-to-liver background ratio in the TG animals, compared with the SG animals, was significantly reduced as early as 24 h after treatment (P = 0.01) and remained reduced at 1 wk (P = 0.003). Tumor SUVmax increased from the baseline levels at 7 d in controls (P = 0.05). The histopathologic analysis of explanted livers revealed increased tumor necrosis in all TG samples. There was a significant inverse correlation (r2 = 0.538, P = 0.005) between the percentage of tumor necrosis on histopathology and tumor SUVmax on 18F-FDG PET at 7 d after treatment with 3-BrPA. Conclusion: Intraarterial injection of 3-BrPA resulted in markedly decreased 18F-FDG uptake as imaged by PET/CT and increased tumor necrosis on histopathology at 1 wk after treatment in the VX2 rabbit liver tumor. PET/CT appears to be a useful means to follow antiglycolytic therapy with 3-BrPA.

AB - The purpose of this study was to determine the effects of 3-bromopyruvate (3-BrPA) on tumor glucose metabolism as imaged with 18F-FDG PET/CT at multiple time points after treatment and compare them with those after intraarterial control injections of saline. Methods: Twenty-three New Zealand White rabbits implanted intrahepatically with VX2 tumors were assigned to 1 of 2 groups: 14 rabbits were assigned to the treatment group (TG) and 9 to the saline control group (SG). All animals were infused with 25 mL of either 1.75 mM 3-BrPA or saline over 1 h via a 2-French catheter, which was secured in the hepatic artery. For PET/CT, the animals were injected with 37 MBq of 18F-FDG at 1 d before treatment and 2 h, 24 h, and 1 wk after treatment. Tumor size, tumor and liver maximal standardized uptake value (SUVmax), and tumor-to-background ratios were calculated for all studies. Seven TG and 5 SG animals were sacrificed at 1 wk after treatment for histopathologic analysis. Results: Intense 18F-FDG uptake was seen in untreated tumors. A significant reduction in tumor SUVmax was noted in TG animals, when compared with SG animals, at 1 wk after treatment (P = 0.006). The tumor-to-liver background ratio in the TG animals, compared with the SG animals, was significantly reduced as early as 24 h after treatment (P = 0.01) and remained reduced at 1 wk (P = 0.003). Tumor SUVmax increased from the baseline levels at 7 d in controls (P = 0.05). The histopathologic analysis of explanted livers revealed increased tumor necrosis in all TG samples. There was a significant inverse correlation (r2 = 0.538, P = 0.005) between the percentage of tumor necrosis on histopathology and tumor SUVmax on 18F-FDG PET at 7 d after treatment with 3-BrPA. Conclusion: Intraarterial injection of 3-BrPA resulted in markedly decreased 18F-FDG uptake as imaged by PET/CT and increased tumor necrosis on histopathology at 1 wk after treatment in the VX2 rabbit liver tumor. PET/CT appears to be a useful means to follow antiglycolytic therapy with 3-BrPA.

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KW - Hepatology

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KW - Liver cancer

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