(99m)Tc-EC-guanine: synthesis, biodistribution, and tumor imaging in animals

• Published in: Pharmaceutical research Vol. 22; no. 9; pp. 1471 - 1479
• Main Authors: Yang, David J, Ozaki, Kaoru, Oh, Chang-Sok, Azhdarinia, Ali, Yang, Thomas, Ito, Megumi, Greenwell, Allison, Bryant, Jerry, Kohanim, Saady, Wong, Vincenzo K, Kim, E Edmund
• Format: Journal Article
• Language: English
• Published: United States 01.09.2005
• Subjects: Animals; Autoradiography; Cell Cycle; Guanine - analogs & derivatives; Guanine - chemical synthesis; Guanine - pharmacokinetics; Humans; Male; Organotechnetium Compounds - chemical synthesis; Organotechnetium Compounds - pharmacokinetics; Prostatic Neoplasms - diagnostic imaging; Prostatic Neoplasms - enzymology; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Radionuclide Imaging; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - pharmacokinetics; Rats; Rats, Sprague-Dawley; Simplexvirus - enzymology; Thymidine Kinase - genetics; Thymidine Kinase - metabolism; Tissue Distribution; Tomography, Emission-Computed, Single-Photon; Tumor Cells, Cultured
• ISSN: 0724-8741
• DOI: 10.1007/s11095-005-6157-8

DNA markers are useful in assessing cell proliferation. The purpose of this study was to synthesize (99m)Tc-ethylenedicysteine-guanine (EC-Guan) for evaluation of cell proliferation. Tumor cells were incubated with (99m)Tc-EC-Guan for cell cycle analysis. Prostate tumor cells that were overexpressing the HSV thymidine kinase gene, or various tumor cells were incubated with (99m)Tc-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 (99m)Tc-EC-Guan and (99m)Tc-EC (control) were determined in tumor-bearing rodents at 0.5-4 h. 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 (99m)Tc-EC-Guan showed increased tumor/tissue count density ratios as a function of time. Our results indicate that (99m)Tc-EC-Guan may be useful as a tumor proliferation imaging agent.