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99mTc-EC-Guanine: Synthesis, Biodistribution, and Tumor Imaging in Animals

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Purpose

DNA markers are useful in assessing cell proliferation. The purpose of this study was to synthesize 99mTc-ethylenedicysteine-guanine (EC-Guan) for evaluation of cell proliferation.

Methods

Tumor cells were incubated with 99mTc-EC-Guan for cell cycle analysis. Prostate tumor cells that were overexpressing the HSV thymidine kinase gene, or various tumor cells were incubated with 99mTc-EC-Guan at 0.5–2 h. Thymidine incorporation assays were performed in lung cancer cells incubated with EC-Guan at 0.1–1 mg/well. Tissue distribution, autoradiography, and planar scintigraphy of 99mTc-EC-Guan and 99mTc-EC (control) were determined in tumor-bearing rodents at 0.5–4 h.

Results

Cell culture assays indicated that EC-Guan was incorporated in DNA, and there was no significant uptake difference between HSVTK overexpressed and normal groups. Biodistribution and scintigraphic imaging studies of 99mTc-EC-Guan showed increased tumor/tissue count density ratios as a function of time.

Conclusions

Our results indicate that 99mTc-EC-Guan may be useful as a tumor proliferation imaging agent.

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Abbreviations

EC:

ethylenedicysteine

FDG:

Fluorodeoxyglucose

FLT:

Fluoro-L thymidine

Guan:

guanine

PET:

positron emission tomography

SPECT:

single photon emission computed tomography

Tk:

thymidine kinase

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Acknowledgments

The authors wish to thank Eloise Daigle for her secretarial support. This work was supported in part by Cell>Point L.L.C (MDA LS01-212) and the John S. Dunn Foundation. The animal research and NMR facility was supported by M. D. Anderson Cancer Center (CORE) Grant NIH CA-16672.

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Authors and Affiliations

  1. Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas, 77030, USA

    David J. Yang, Kaoru Ozaki, Chang-Sok Oh, Ali Azhdarinia, Thomas Yang, Megumi Ito, Allison Greenwell, Jerry Bryant, Saady Kohanim, Vincenzo K. Wong & E. Edmund Kim

  2. Department of Experimental Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas, 77030, USA

    David J. Yang

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  1. David J. Yang
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Correspondence to David J. Yang.

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Yang, D.J., Ozaki, K., Oh, CS. et al. 99mTc-EC-Guanine: Synthesis, Biodistribution, and Tumor Imaging in Animals. Pharm Res 22, 1471–1479 (2005). https://doi.org/10.1007/s11095-005-6157-8

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  • DOI: https://doi.org/10.1007/s11095-005-6157-8

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