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99M Tc‐C‐Deoxyglucose: Synthesis, cellular uptake, biodistribution and scintigraphic imaging
Author(s) -
Yang D. J.,
Azhdarinia A.,
Yu DF,
Kim E. E.,
Podoloff D. A.
Publication year - 2001
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.25804401182
Subject(s) - biodistribution , deoxyglucose , chemistry , insulin , in vivo , glucose uptake , glucosamine , in vitro , radiochemistry , endocrinology , biochemistry , medicine , microbiology and biotechnology , biology
This study was aimed to synthesize 99m Tc‐ethylenedicysteine‐deoxyglucose (EC‐DG) and determine in vitro cellular uptake and in vivo biodistribution and imaging feasibility in tumor‐bearing rodents. Experimental: Synthesis of EC‐deoxyglucose (EC‐DG) was carried out by reacting EC with glucosamine using carbodiimide as a coupling agent. After dialysis the chemical yield was 70%. By adding pertechnetate in the presence of tin chloride (0.1 mg) to EC‐DG (20–100 mg), the radiochemical yield was achieved 70–100% as determined by radio‐TLC. Hexokinase assays of EC‐DG were performed at UV wavelength 340 nm. In vitro cellular uptake assay was conducted by using a human lung cancer cell line (A549). Each well containing 80,000 cells was added d‐ and 1‐glucose (1 mg and 2.0 mg) along with 2μCi of 99m Tc‐EC‐deoxyglucose and 18 F‐FDG. After incubation, the cells were washed. A gamma counter counted the cells. To determine whether blood glucose level could be induced by EC‐DG and suppressed by insulin, normal Fischer 344 rats were fasting overnight prior to the experiments. The baseline of blood glucose level (mg/dl) was measured by a glucose meter. Each rat was administered 1.2 mmol/kg (i.v.) of glucosamine, FDG and EC‐deoxyglucose. In a separate experiment, rats were administered EC‐DG and FDG, and then insulin (5 units) was administered after 30 minutes. Blood samples were collected from tail vein every 30‐min up to 6 hrs post‐administration. For breast tumor‐bearing animal model, female Fischer 344 rats (150±25 g) were inoculated with tumor cells (10 6 cells/rat, s.c. derived from DMBA‐induced tumor cell line) into the hind legs. For lung tumor‐bearing animal model, each athymic nude mouse (20–25g) was inoculated (s.c.) with 0.1 ml of human lung tumor cells from the A549 tumor cell line suspension into the hind legs. Studies performed 17 to 21 days after implantation when tumors reached approximately 0.6–1.0 cm diameter. Each animal was injected (i.v.) with 10 μCi (per rat) or 1 μCi (per mouse) of 99m Tc‐EC, 99m Tc‐EC‐DG and FDG (standard) (n=3/time point). The injected mass of 99m Tc‐EC‐DG was 1 mg per rodent. Following administration of the radiotracers, the rodents were sacrificed at 0.5–4 hrs and the selected tissues were excised, weighed and counted for radioactivity. Scintigraphic images were obtained 0.5–4 hours after i.v. injection of 100 μCi of the radiotracer. Results: EC‐DG showed positive hexokinase assay. By adding d‐glucose, a decreased uptake of 99m Tc‐EC‐DG and 18 F‐FDG was observed. Blood glucose level was induced by glucosamine, FDG and EC‐DG. This increased blood glucose level could be suppressed by co‐administration of EC‐DG or FDG and insulin. Compare to 99m Tc‐EC and free 99m Tc, tumor‐to tissue count density ratios increased as a function of time in 99m Tc‐EC‐DG group. Brain and heart uptake was less than FDG. Tumor/brain and tumor/muscle ratios were higher than FDG. Tumor could be visualized well when compared to 99m Tc‐EC (control group).