Evaluation of F-18-labeled 5-iodocytidine ( 18F-FIAC) as a new potential positron emission tomography probe for herpes simplex virus type 1 thymidine kinase imaging

Pei Chia Chan; Chun Yi Wu; Wen Yi Chang; Wei Ting Chang; Mian Alauddin; Ren Shan Liu; Wuu Jyh Lin; Fu Du Chen; Chuan Lin Chen; Hsin Ell Wang

doi:10.1016/j.nucmedbio.2011.04.003

Evaluation of F-18-labeled 5-iodocytidine ( ¹⁸F-FIAC) as a new potential positron emission tomography probe for herpes simplex virus type 1 thymidine kinase imaging

Pei Chia Chan, Chun Yi Wu, Wen Yi Chang, Wei Ting Chang, Mian Alauddin, Ren Shan Liu, Wuu Jyh Lin, Fu Du Chen, Chuan Lin Chen, Hsin Ell Wang

Cancer Systems Imaging

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Objective: Herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene in combination with radiolabeled nucleoside substrates is the most widely used reporter system. This study characterized 1-(2'-deoxy-2'-[ ¹⁸F]fluoro-β-d-arabinofuranosyl)-5-iodocytosine ( ¹⁸F-FIAC) as a new potential positron emission tomography (PET) probe for HSV1-tk gene imaging and compared it with 2'-deoxy-2'-[ ¹⁸F]fluoro-5-iodo-1-β-D-arabinofuranosyluracil ( ¹⁸F-FIAU) and 2'-deoxy-2'-[ ¹⁸F]fluoro-5-ethyl-1-β-D-arabinofuranosyluracil( ¹⁸F-FEAU) (thymidine analogues) in an NG4TL4-WT/STK sarcoma-bearing mouse model. Methods: A cellular uptake assay, biodistribution study, radioactive metabolites assay and microPET imaging of NG4TL4-WT/STK tumor-bearing mice post administration of ¹⁸F-FIAC, ¹⁸F-FIAU and ¹⁸F-FEAU were conducted to characterize the biological properties of these tracers. Results: Highly specific uptake of ¹⁸F-FIAC, ¹⁸F-FIAU and ¹⁸F-FEAU in tk-transfected [tk(+)] cells was observed. The tk(+)-to-tk(-) cellular uptake ratio after a 2-h incubation was 66.6±25.1, 76.3±18.2 and 247.2±37.2, respectively. In biodistribution studies, ¹⁸F-FIAC showed significant tk(+) tumor specificity (12.6; expressed as the tk(+)-to-tk(-) tumor uptake ratio at 2 h postinjection) comparable with ¹⁸F-FIAU (15.8) but lower than ¹⁸F-FEAU (48.0). The results of microPET imaging also revealed the highly specific accumulation of these three radioprobes in the NG4TL4-tk(+) tumor. Conclusion: Our findings suggested that the cytidine analogue ¹⁸F-FIAC is a new potential PET probe for the imaging of HSV1-tk gene expression. ¹⁸F-FIAC may be regarded as the prodrug of ¹⁸F-FIAU in vivo.

Original language	English (US)
Pages (from-to)	987-995
Number of pages	9
Journal	Nuclear Medicine and Biology
Volume	38
Issue number	7
DOIs	https://doi.org/10.1016/j.nucmedbio.2011.04.003
State	Published - Oct 2011

Keywords

F-FEAU
F-FIAC
HSV1-tk
MicroPET
Nucleoside
Reporter probe

ASJC Scopus subject areas

Molecular Medicine
Radiology Nuclear Medicine and imaging
Cancer Research

Access to Document

10.1016/j.nucmedbio.2011.04.003

Cite this

Chan, P. C., Wu, C. Y., Chang, W. Y., Chang, W. T., Alauddin, M., Liu, R. S., Lin, W. J., Chen, F. D., Chen, C. L., & Wang, H. E. (2011). Evaluation of F-18-labeled 5-iodocytidine ( ¹⁸F-FIAC) as a new potential positron emission tomography probe for herpes simplex virus type 1 thymidine kinase imaging. Nuclear Medicine and Biology, 38(7), 987-995. https://doi.org/10.1016/j.nucmedbio.2011.04.003

Chan, PC, Wu, CY, Chang, WY, Chang, WT, Alauddin, M, Liu, RS, Lin, WJ, Chen, FD, Chen, CL & Wang, HE 2011, 'Evaluation of F-18-labeled 5-iodocytidine ( ¹⁸F-FIAC) as a new potential positron emission tomography probe for herpes simplex virus type 1 thymidine kinase imaging', Nuclear Medicine and Biology, vol. 38, no. 7, pp. 987-995. https://doi.org/10.1016/j.nucmedbio.2011.04.003

@article{6ec0c6bcc91647d19f30923c04340dd7,

title = "Evaluation of F-18-labeled 5-iodocytidine ( 18F-FIAC) as a new potential positron emission tomography probe for herpes simplex virus type 1 thymidine kinase imaging",

abstract = "Objective: Herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene in combination with radiolabeled nucleoside substrates is the most widely used reporter system. This study characterized 1-(2'-deoxy-2'-[ 18F]fluoro-β-d-arabinofuranosyl)-5-iodocytosine ( 18F-FIAC) as a new potential positron emission tomography (PET) probe for HSV1-tk gene imaging and compared it with 2'-deoxy-2'-[ 18F]fluoro-5-iodo-1-β-D-arabinofuranosyluracil ( 18F-FIAU) and 2'-deoxy-2'-[ 18F]fluoro-5-ethyl-1-β-D-arabinofuranosyluracil( 18F-FEAU) (thymidine analogues) in an NG4TL4-WT/STK sarcoma-bearing mouse model. Methods: A cellular uptake assay, biodistribution study, radioactive metabolites assay and microPET imaging of NG4TL4-WT/STK tumor-bearing mice post administration of 18F-FIAC, 18F-FIAU and 18F-FEAU were conducted to characterize the biological properties of these tracers. Results: Highly specific uptake of 18F-FIAC, 18F-FIAU and 18F-FEAU in tk-transfected [tk(+)] cells was observed. The tk(+)-to-tk(-) cellular uptake ratio after a 2-h incubation was 66.6±25.1, 76.3±18.2 and 247.2±37.2, respectively. In biodistribution studies, 18F-FIAC showed significant tk(+) tumor specificity (12.6; expressed as the tk(+)-to-tk(-) tumor uptake ratio at 2 h postinjection) comparable with 18F-FIAU (15.8) but lower than 18F-FEAU (48.0). The results of microPET imaging also revealed the highly specific accumulation of these three radioprobes in the NG4TL4-tk(+) tumor. Conclusion: Our findings suggested that the cytidine analogue 18F-FIAC is a new potential PET probe for the imaging of HSV1-tk gene expression. 18F-FIAC may be regarded as the prodrug of 18F-FIAU in vivo.",

keywords = "F-FEAU, F-FIAC, HSV1-tk, MicroPET, Nucleoside, Reporter probe",

author = "Chan, {Pei Chia} and Wu, {Chun Yi} and Chang, {Wen Yi} and Chang, {Wei Ting} and Mian Alauddin and Liu, {Ren Shan} and Lin, {Wuu Jyh} and Chen, {Fu Du} and Chen, {Chuan Lin} and Wang, {Hsin Ell}",

note = "Funding Information: This study was supported by grants from the National Science Council, Taiwan ( NSC96-2321-B-010-003-MY2, NSC96-2623-7-010-002-NU and 99-3112-B-010-015 ). We thank the staff of the Molecular and Genetic Imaging Core/National Research Program for Genomic Medicine (NRPGM) who kindly provided the radioisotope and excellent technical assistance. The Institute of Nuclear Energy Research, Taoyuan, is also gratefully acknowledged. No competing financial conflicts exist for any of the authors.",

year = "2011",

month = oct,

doi = "10.1016/j.nucmedbio.2011.04.003",

language = "English (US)",

volume = "38",

pages = "987--995",

journal = "Nuclear Medicine and Biology",

issn = "0969-8051",

publisher = "Elsevier Inc.",

number = "7",

}

TY - JOUR

T1 - Evaluation of F-18-labeled 5-iodocytidine ( 18F-FIAC) as a new potential positron emission tomography probe for herpes simplex virus type 1 thymidine kinase imaging

AU - Chan, Pei Chia

AU - Wu, Chun Yi

AU - Chang, Wen Yi

AU - Chang, Wei Ting

AU - Alauddin, Mian

AU - Liu, Ren Shan

AU - Lin, Wuu Jyh

AU - Chen, Fu Du

AU - Chen, Chuan Lin

AU - Wang, Hsin Ell

N1 - Funding Information: This study was supported by grants from the National Science Council, Taiwan ( NSC96-2321-B-010-003-MY2, NSC96-2623-7-010-002-NU and 99-3112-B-010-015 ). We thank the staff of the Molecular and Genetic Imaging Core/National Research Program for Genomic Medicine (NRPGM) who kindly provided the radioisotope and excellent technical assistance. The Institute of Nuclear Energy Research, Taoyuan, is also gratefully acknowledged. No competing financial conflicts exist for any of the authors.

PY - 2011/10

Y1 - 2011/10

N2 - Objective: Herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene in combination with radiolabeled nucleoside substrates is the most widely used reporter system. This study characterized 1-(2'-deoxy-2'-[ 18F]fluoro-β-d-arabinofuranosyl)-5-iodocytosine ( 18F-FIAC) as a new potential positron emission tomography (PET) probe for HSV1-tk gene imaging and compared it with 2'-deoxy-2'-[ 18F]fluoro-5-iodo-1-β-D-arabinofuranosyluracil ( 18F-FIAU) and 2'-deoxy-2'-[ 18F]fluoro-5-ethyl-1-β-D-arabinofuranosyluracil( 18F-FEAU) (thymidine analogues) in an NG4TL4-WT/STK sarcoma-bearing mouse model. Methods: A cellular uptake assay, biodistribution study, radioactive metabolites assay and microPET imaging of NG4TL4-WT/STK tumor-bearing mice post administration of 18F-FIAC, 18F-FIAU and 18F-FEAU were conducted to characterize the biological properties of these tracers. Results: Highly specific uptake of 18F-FIAC, 18F-FIAU and 18F-FEAU in tk-transfected [tk(+)] cells was observed. The tk(+)-to-tk(-) cellular uptake ratio after a 2-h incubation was 66.6±25.1, 76.3±18.2 and 247.2±37.2, respectively. In biodistribution studies, 18F-FIAC showed significant tk(+) tumor specificity (12.6; expressed as the tk(+)-to-tk(-) tumor uptake ratio at 2 h postinjection) comparable with 18F-FIAU (15.8) but lower than 18F-FEAU (48.0). The results of microPET imaging also revealed the highly specific accumulation of these three radioprobes in the NG4TL4-tk(+) tumor. Conclusion: Our findings suggested that the cytidine analogue 18F-FIAC is a new potential PET probe for the imaging of HSV1-tk gene expression. 18F-FIAC may be regarded as the prodrug of 18F-FIAU in vivo.

AB - Objective: Herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene in combination with radiolabeled nucleoside substrates is the most widely used reporter system. This study characterized 1-(2'-deoxy-2'-[ 18F]fluoro-β-d-arabinofuranosyl)-5-iodocytosine ( 18F-FIAC) as a new potential positron emission tomography (PET) probe for HSV1-tk gene imaging and compared it with 2'-deoxy-2'-[ 18F]fluoro-5-iodo-1-β-D-arabinofuranosyluracil ( 18F-FIAU) and 2'-deoxy-2'-[ 18F]fluoro-5-ethyl-1-β-D-arabinofuranosyluracil( 18F-FEAU) (thymidine analogues) in an NG4TL4-WT/STK sarcoma-bearing mouse model. Methods: A cellular uptake assay, biodistribution study, radioactive metabolites assay and microPET imaging of NG4TL4-WT/STK tumor-bearing mice post administration of 18F-FIAC, 18F-FIAU and 18F-FEAU were conducted to characterize the biological properties of these tracers. Results: Highly specific uptake of 18F-FIAC, 18F-FIAU and 18F-FEAU in tk-transfected [tk(+)] cells was observed. The tk(+)-to-tk(-) cellular uptake ratio after a 2-h incubation was 66.6±25.1, 76.3±18.2 and 247.2±37.2, respectively. In biodistribution studies, 18F-FIAC showed significant tk(+) tumor specificity (12.6; expressed as the tk(+)-to-tk(-) tumor uptake ratio at 2 h postinjection) comparable with 18F-FIAU (15.8) but lower than 18F-FEAU (48.0). The results of microPET imaging also revealed the highly specific accumulation of these three radioprobes in the NG4TL4-tk(+) tumor. Conclusion: Our findings suggested that the cytidine analogue 18F-FIAC is a new potential PET probe for the imaging of HSV1-tk gene expression. 18F-FIAC may be regarded as the prodrug of 18F-FIAU in vivo.

KW - F-FEAU

KW - F-FIAC

KW - HSV1-tk

KW - MicroPET

KW - Nucleoside

KW - Reporter probe

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