Herpes simplex virus thymidine kinase imaging in mice with (1-(2′-deoxy-2′-[18F]fluoro-1-β-D-arabinofuranosyl)- 5-iodouracil) and metabolite (1-(2′-deoxy-2′-[18F]fluoro- 1-β-D-arabinofuranosyl)-5-uracil)

Sridhar Nimmagadda, Thomas J. Mangner, Jawana M. Lawhorn-Crews, Uwe Haberkorn, Anthony F. Shields

Research output: Contribution to journalArticle

Abstract

Purpose: FIAU, (1-(2′-deoxy-2′-fluoro-1-β-D- arabinofuranosyl)-5-iodouracil) has been used as a substrate for herpes simplex virus thymidine kinases (HSV-TK and HSV-tk, for protein and gene expression, respectively) and other bacterial and viral thymidine kinases for noninvasive imaging applications. Previous studies have reported the formation of a de-iodinated metabolite of 18F-FIAU. This study reports the dynamic tumor uptake, biodistribution, and metabolite contribution to the activity of 18F-FIAU seen in HSV-tk gene expressing tumors and compares the distribution properties with its de-iodinated metabolite 18F-FAU. Methods: CD-1 nu/nu mice with subcutaneous MH3924A and MH3924A-stb-tk+ xenografts on opposite flanks were used for the biodistribution and imaging studies. Mice were injected IV with either 18F-FIAU or 18F-FAU. Mice underwent dynamic imaging with each tracer for 65 min followed by additional static imaging up to 150 min post-injection for some animals. Animals were sacrificed at 60 or 150 min post-injection. Samples of blood and tissue were collected for biodistribution and metabolite analysis. Regions of interest were drawn over the images obtained from both tumors to calculate the time-activity curves. Results: Biodistribution and imaging studies showed the highest uptake of 18F-FIAU in the MH3924A-stb-tk+ tumors. Dynamic imaging studies revealed a continuous accumulation of 18F-FIAU in HSV-TK expressing tumors over 60 min. The mean biodistribution values (SUV ± SE) for MH3924A-stb-tk+ were 2.07±0.40 and 6.15±1.58 and that of MH3924A tumors were 0.19±0.07 and 0.47±0.06 at 60 and 150 min, respectively. In 18F-FIAU injected mice, at 60 min nearly 63% of blood activity was present as its metabolite 18F-FAU. Imaging and biodistribution studies with 18F-FAU demonstrated no specific accumulation in MH3924A-stb-tk+ tumors and SUVs for both the tumors were similar to those observed with muscle. Conclusion: 18F-FIAU shows a continuous accumulation of activity in HSV-TK expressing tumors. 18F-FAU does not show any preferential accumulation in HSV-TK expressing tumors. In the 18F-FIAU treated mice, the 18F-FAU contribution to the total uptake seen in HSV-TK positive tumors is minimal.

Original languageEnglish (US)
Pages (from-to)1987-1993
Number of pages7
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume36
Issue number12
DOIs
StatePublished - Dec 2009
Externally publishedYes

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Thymidine Kinase
Simplexvirus
Neoplasms
5-iodouracil
1-(2'-deoxy-2'-fluoro-1-arabinofuranosyl)-5-uracil
fialuridine
Injections
Heterografts
Gene Expression

Keywords

  • F
  • FIAU
  • Gene expression
  • HSV-TK
  • Metabolism
  • PET imaging

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

@article{194590d8202640e4948e74325d08ccb1,
title = "Herpes simplex virus thymidine kinase imaging in mice with (1-(2′-deoxy-2′-[18F]fluoro-1-β-D-arabinofuranosyl)- 5-iodouracil) and metabolite (1-(2′-deoxy-2′-[18F]fluoro- 1-β-D-arabinofuranosyl)-5-uracil)",
abstract = "Purpose: FIAU, (1-(2′-deoxy-2′-fluoro-1-β-D- arabinofuranosyl)-5-iodouracil) has been used as a substrate for herpes simplex virus thymidine kinases (HSV-TK and HSV-tk, for protein and gene expression, respectively) and other bacterial and viral thymidine kinases for noninvasive imaging applications. Previous studies have reported the formation of a de-iodinated metabolite of 18F-FIAU. This study reports the dynamic tumor uptake, biodistribution, and metabolite contribution to the activity of 18F-FIAU seen in HSV-tk gene expressing tumors and compares the distribution properties with its de-iodinated metabolite 18F-FAU. Methods: CD-1 nu/nu mice with subcutaneous MH3924A and MH3924A-stb-tk+ xenografts on opposite flanks were used for the biodistribution and imaging studies. Mice were injected IV with either 18F-FIAU or 18F-FAU. Mice underwent dynamic imaging with each tracer for 65 min followed by additional static imaging up to 150 min post-injection for some animals. Animals were sacrificed at 60 or 150 min post-injection. Samples of blood and tissue were collected for biodistribution and metabolite analysis. Regions of interest were drawn over the images obtained from both tumors to calculate the time-activity curves. Results: Biodistribution and imaging studies showed the highest uptake of 18F-FIAU in the MH3924A-stb-tk+ tumors. Dynamic imaging studies revealed a continuous accumulation of 18F-FIAU in HSV-TK expressing tumors over 60 min. The mean biodistribution values (SUV ± SE) for MH3924A-stb-tk+ were 2.07±0.40 and 6.15±1.58 and that of MH3924A tumors were 0.19±0.07 and 0.47±0.06 at 60 and 150 min, respectively. In 18F-FIAU injected mice, at 60 min nearly 63{\%} of blood activity was present as its metabolite 18F-FAU. Imaging and biodistribution studies with 18F-FAU demonstrated no specific accumulation in MH3924A-stb-tk+ tumors and SUVs for both the tumors were similar to those observed with muscle. Conclusion: 18F-FIAU shows a continuous accumulation of activity in HSV-TK expressing tumors. 18F-FAU does not show any preferential accumulation in HSV-TK expressing tumors. In the 18F-FIAU treated mice, the 18F-FAU contribution to the total uptake seen in HSV-TK positive tumors is minimal.",
keywords = "F, FIAU, Gene expression, HSV-TK, Metabolism, PET imaging",
author = "Sridhar Nimmagadda and Mangner, {Thomas J.} and Lawhorn-Crews, {Jawana M.} and Uwe Haberkorn and Shields, {Anthony F.}",
year = "2009",
month = "12",
doi = "10.1007/s00259-009-1177-y",
language = "English (US)",
volume = "36",
pages = "1987--1993",
journal = "European Journal of Nuclear Medicine and Molecular Imaging",
issn = "1619-7070",
publisher = "Springer Verlag",
number = "12",

}

TY - JOUR

T1 - Herpes simplex virus thymidine kinase imaging in mice with (1-(2′-deoxy-2′-[18F]fluoro-1-β-D-arabinofuranosyl)- 5-iodouracil) and metabolite (1-(2′-deoxy-2′-[18F]fluoro- 1-β-D-arabinofuranosyl)-5-uracil)

AU - Nimmagadda, Sridhar

AU - Mangner, Thomas J.

AU - Lawhorn-Crews, Jawana M.

AU - Haberkorn, Uwe

AU - Shields, Anthony F.

PY - 2009/12

Y1 - 2009/12

N2 - Purpose: FIAU, (1-(2′-deoxy-2′-fluoro-1-β-D- arabinofuranosyl)-5-iodouracil) has been used as a substrate for herpes simplex virus thymidine kinases (HSV-TK and HSV-tk, for protein and gene expression, respectively) and other bacterial and viral thymidine kinases for noninvasive imaging applications. Previous studies have reported the formation of a de-iodinated metabolite of 18F-FIAU. This study reports the dynamic tumor uptake, biodistribution, and metabolite contribution to the activity of 18F-FIAU seen in HSV-tk gene expressing tumors and compares the distribution properties with its de-iodinated metabolite 18F-FAU. Methods: CD-1 nu/nu mice with subcutaneous MH3924A and MH3924A-stb-tk+ xenografts on opposite flanks were used for the biodistribution and imaging studies. Mice were injected IV with either 18F-FIAU or 18F-FAU. Mice underwent dynamic imaging with each tracer for 65 min followed by additional static imaging up to 150 min post-injection for some animals. Animals were sacrificed at 60 or 150 min post-injection. Samples of blood and tissue were collected for biodistribution and metabolite analysis. Regions of interest were drawn over the images obtained from both tumors to calculate the time-activity curves. Results: Biodistribution and imaging studies showed the highest uptake of 18F-FIAU in the MH3924A-stb-tk+ tumors. Dynamic imaging studies revealed a continuous accumulation of 18F-FIAU in HSV-TK expressing tumors over 60 min. The mean biodistribution values (SUV ± SE) for MH3924A-stb-tk+ were 2.07±0.40 and 6.15±1.58 and that of MH3924A tumors were 0.19±0.07 and 0.47±0.06 at 60 and 150 min, respectively. In 18F-FIAU injected mice, at 60 min nearly 63% of blood activity was present as its metabolite 18F-FAU. Imaging and biodistribution studies with 18F-FAU demonstrated no specific accumulation in MH3924A-stb-tk+ tumors and SUVs for both the tumors were similar to those observed with muscle. Conclusion: 18F-FIAU shows a continuous accumulation of activity in HSV-TK expressing tumors. 18F-FAU does not show any preferential accumulation in HSV-TK expressing tumors. In the 18F-FIAU treated mice, the 18F-FAU contribution to the total uptake seen in HSV-TK positive tumors is minimal.

AB - Purpose: FIAU, (1-(2′-deoxy-2′-fluoro-1-β-D- arabinofuranosyl)-5-iodouracil) has been used as a substrate for herpes simplex virus thymidine kinases (HSV-TK and HSV-tk, for protein and gene expression, respectively) and other bacterial and viral thymidine kinases for noninvasive imaging applications. Previous studies have reported the formation of a de-iodinated metabolite of 18F-FIAU. This study reports the dynamic tumor uptake, biodistribution, and metabolite contribution to the activity of 18F-FIAU seen in HSV-tk gene expressing tumors and compares the distribution properties with its de-iodinated metabolite 18F-FAU. Methods: CD-1 nu/nu mice with subcutaneous MH3924A and MH3924A-stb-tk+ xenografts on opposite flanks were used for the biodistribution and imaging studies. Mice were injected IV with either 18F-FIAU or 18F-FAU. Mice underwent dynamic imaging with each tracer for 65 min followed by additional static imaging up to 150 min post-injection for some animals. Animals were sacrificed at 60 or 150 min post-injection. Samples of blood and tissue were collected for biodistribution and metabolite analysis. Regions of interest were drawn over the images obtained from both tumors to calculate the time-activity curves. Results: Biodistribution and imaging studies showed the highest uptake of 18F-FIAU in the MH3924A-stb-tk+ tumors. Dynamic imaging studies revealed a continuous accumulation of 18F-FIAU in HSV-TK expressing tumors over 60 min. The mean biodistribution values (SUV ± SE) for MH3924A-stb-tk+ were 2.07±0.40 and 6.15±1.58 and that of MH3924A tumors were 0.19±0.07 and 0.47±0.06 at 60 and 150 min, respectively. In 18F-FIAU injected mice, at 60 min nearly 63% of blood activity was present as its metabolite 18F-FAU. Imaging and biodistribution studies with 18F-FAU demonstrated no specific accumulation in MH3924A-stb-tk+ tumors and SUVs for both the tumors were similar to those observed with muscle. Conclusion: 18F-FIAU shows a continuous accumulation of activity in HSV-TK expressing tumors. 18F-FAU does not show any preferential accumulation in HSV-TK expressing tumors. In the 18F-FIAU treated mice, the 18F-FAU contribution to the total uptake seen in HSV-TK positive tumors is minimal.

KW - F

KW - FIAU

KW - Gene expression

KW - HSV-TK

KW - Metabolism

KW - PET imaging

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U2 - 10.1007/s00259-009-1177-y

DO - 10.1007/s00259-009-1177-y

M3 - Article

VL - 36

SP - 1987

EP - 1993

JO - European Journal of Nuclear Medicine and Molecular Imaging

JF - European Journal of Nuclear Medicine and Molecular Imaging

SN - 1619-7070

IS - 12

ER -