SPECT Imaging of Herpes Simplex Virus Type1 Thymidine Kinase Gene Expression By [123I]FIAU1

Choi, Seok; Zhuang, Zhi Ping; Chacko, Ann‐Marie; Acton, Paul D.; Tjuvajev-Gelovani, Juri; Doubrovin, Mikhail; Chu, David C. K.; Kung, Hank F.

doi:10.1016/j.acra.2005.04.010

Cited by 23 publications

(15 citation statements)

References 30 publications

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“…Herpes simplex virus type 1 thymidine kinase (hsvTK) and mutant hsv1sr39TK reporter genes have been used in most of these seminal studies. Radiolabeled reporter probes, including 1-(2-deoxy-2-fluoro-1-D-arabinofuranosyl)-5-iodouracil (FIAU) (labeled with 131 I ( 5 ), 123 I ( 5 ), 124 I ( 6 ), and 125 I ( 7 )), 29- 18 F-fluoro-5-ethyl-1-β-D-arabinofuranosyluracil ( 18 F-FEAU) ( 8 ), and 9-(4- 18 F-fluoro-3-[hydroxymethyl] butyl)guanine ( 18 F-FHBG) ( 9 ) have been used for imaging hsvTK in these studies, and comparisons of their efficacy have previously been performed ( 10–12 ). However, there has been a recent focus on human reporter systems, to avoid the potential risk of generating an immunologic reaction to viral (nonhuman) reporter systems, including hsvTK and hsvsr39TK reporter–transduced T cells.…”

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confidence: 99%

Comparative Analysis of T Cell Imaging with Human Nuclear Reporter Genes

et al. 2015

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Monitoring genetically altered T cells is an important component of adoptive T cell therapy in patients, and the ability to visualize their trafficking/targeting, proliferation/expansion, and retention/death using highly sensitive reporter systems that do not induce an immunologic response would provide useful information. Therefore, we focused on human reporter gene systems that have the potential for translation to clinical studies. The objective of the in vivo imaging studies was to determine the minimum number of T cells that could be visualized with the different nuclear reporter systems. We determined the imaging sensitivity (lower limit of T cell detection) of each reporter using appropriate radiolabeled probes for PET or SPECT imaging. Methods Human T cells were transduced with retroviral vectors encoding for the human norepinephrine transporter (hNET), human sodiumiodide symporter (hNIS), a human deoxycytidine kinase double mutant (hdCKDM), and herpes simplex virus type 1 thymidine kinase (hsvTK) reporter genes. After viability and growth were assessed, 105 to 3 × 106 reporter T cells were injected subcutaneously on the shoulder area. The corresponding radiolabeled probe was injected intravenously 30 min later, followed by sequential PET or SPECT imaging. Radioactivity at the T cell injection sites and in the thigh (back-ground) was measured. Results The viability and growth of experimental cells were unaffected by transduction. The hNET/meta-18F-fluorobenzylguanidine (18F-MFBG) reporter system could detect less than 1 × 105 T cells because of its high uptake in the transduced T cells and low background activity. The hNIS/124I-iodide reporter system could detect approximately 1 × 106 T cells; 124I-iodide uptake at the T cell injection site was time-dependent and associated with high background. The hdCKDM/2′-18F-fluoro-5-ethyl-1-β-D-arabinofuranosyluracil (18F-FEAU) and hsvTK/18F-FEAU reporter systems detected approximately 3 × 105 T cells, respectively. 18F-FEAU was a more efficient probe (higher uptake, lower background) than 124I-1-(2-deoxy-2-fluoro-1-D-arabinofuranosyl)-5-iodouracil for both hdCKDM and hsvTK. Conclusion A comparison of different reporter gene–reporter probe systems for imaging of T cell number was performed, and the hNET/18F-MFBG PET reporter system was found to be the most sensitive and capable of detecting approximately 35–40 × 103 T cells at the site of T cell injection in the animal model.

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Comparative Analysis of T Cell Imaging with Human Nuclear Reporter Genes

et al. 2015

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“…[ 125 I]FIAU was prepared by the iododestannylation method as reported previously [24,26]. Briefly, to a solution of 5-tri- n -butylstannyl derivative of FIAU in MeOH was added [ 125 I]NaI, followed by the addition of 30% H 2 O 2 /acetic acid.…”

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confidence: 99%

5-[18F]Fluoroalkyl pyrimidine nucleosides: probes for positron emission tomography imaging of herpes simplex virus type 1 thymidine kinase gene expression

Chacko

Blankemeyer

Lieberman

et al. 2009

Nuclear Medicine and Biology

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“…37,38,48 Non-transduced (wild-type) RG2 cell were used as controls. Cells were cultivated in Dulbecco’s modified Eagle medium (DMEM) supplemented with 10 % fetal bovine serum (FBS) and 1% penicillin/streptomycin.…”

Section: Methodsmentioning

confidence: 99%

Synthesis and in Vitro Evaluation of 5-[¹⁸F]Fluoroalkyl Pyrimidine Nucleosides for Molecular Imaging of Herpes Simplex Virus Type 1 Thymidine Kinase Reporter Gene Expression

2008

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Two novel series of 5-fluoroalkyl-2′-deoxyuridines (FPrDU, FBuDU, FPeDU) and 2′-fluoro-2′-deoxy-5-fluoroalkylarabinouridines (FFPrAU, FFBuAU, FFPeAU), having three, four or five methylene units (propyl, butyl, or pentyl) at C-5, were prepared and tested as reporter probes for imaging HSV1-tk gene expression. The Negishi coupling methodology was employed to efficiently synthesize the radiolabeling precursors. All six 5-[18F]fluoroalkyl pyrimidines were prepared readily from 3-N-benzoyl-3′,5′-di-O-benzoyl-protected 5-O-mesylate precursors in 17–35% radiochemical yield (decay-corrected). In vitro studies highlighted that all six [18F]labeled nucleosides selectively accumulated in cells expressing the HSV1-TK protein, with negligible uptake in control cells. [18F]FPrDU, [18F]FBuDU, [18F]FPeDU, and [18F]FFBuAU had the best uptake profiles. Despite selective accumulation in HSV1-tk expressing cells, all 5-fluoroalkyl pyrimidine nucleosides had low to negligible cytotoxic activity (CC50>1000–209 μM). Ultimately, results demonstrated that 5-[18F]fluoropropyl, [18F]fluorobutyl, and [18F]fluoropentyl pyrimidine nucleosides have potential as in vivo HSV1-TK PET reporter probes over a dynamic range of reporter gene expression levels.

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SPECT Imaging of Herpes Simplex Virus Type1 Thymidine Kinase Gene Expression By [123I]FIAU1

Cited by 23 publications

References 30 publications

Comparative Analysis of T Cell Imaging with Human Nuclear Reporter Genes

Comparative Analysis of T Cell Imaging with Human Nuclear Reporter Genes

5-[18F]Fluoroalkyl pyrimidine nucleosides: probes for positron emission tomography imaging of herpes simplex virus type 1 thymidine kinase gene expression

Synthesis and in Vitro Evaluation of 5-[¹⁸F]Fluoroalkyl Pyrimidine Nucleosides for Molecular Imaging of Herpes Simplex Virus Type 1 Thymidine Kinase Reporter Gene Expression

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SPECT Imaging of Herpes Simplex Virus Type1 Thymidine Kinase Gene Expression By [123I]FIAU1

Cited by 23 publications

References 30 publications

Comparative Analysis of T Cell Imaging with Human Nuclear Reporter Genes

Comparative Analysis of T Cell Imaging with Human Nuclear Reporter Genes

5-[18F]Fluoroalkyl pyrimidine nucleosides: probes for positron emission tomography imaging of herpes simplex virus type 1 thymidine kinase gene expression

Synthesis and in Vitro Evaluation of 5-[18F]Fluoroalkyl Pyrimidine Nucleosides for Molecular Imaging of Herpes Simplex Virus Type 1 Thymidine Kinase Reporter Gene Expression

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Synthesis and in Vitro Evaluation of 5-[¹⁸F]Fluoroalkyl Pyrimidine Nucleosides for Molecular Imaging of Herpes Simplex Virus Type 1 Thymidine Kinase Reporter Gene Expression