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


METHODS
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.


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 (99m)Tc-EC-Guan showed increased tumor/tissue count density ratios as a function of time.


CONCLUSIONS
Our results indicate that (99m)Tc-EC-Guan may be useful as a tumor proliferation imaging agent.
Yang
David J
DJ
Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. dyang@di.mdacc.tmc.edu
Ozaki
Kaoru
K
Oh
Chang-Sok
CS
Azhdarinia
Ali
A
Yang
Thomas
T
Ito
Megumi
M
Greenwell
Allison
A
Bryant
Jerry
J
Kohanim
Saady
S
Wong
Vincenzo K
VK
Kim
E Edmund
EE
D000818:Animals; D001345:Autoradiography; D002453:Cell Cycle; D006147:Guanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018139:Simplexvirus / Q000201:enzymology; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014407:Tumor Cells, Cultured
D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C506601:technetium 99m ethylenedicysteine-9-(4-amino-3-(hydroxymethyl)butyl)guanine conjugate; D006147:Guanine; D013937:Thymidine Kinase