OBJECTIVETo establish a method for detecting plasma concentration of corn polysaccharide iron complex (CPIC) and investigate its absorption, distribution and elimination in rats.

METHODSUsing radioactivity isotope tracing method, we detected the radioactivity of (59)Fe-CPIC in the plasma of rats at different time points by gavages of 3 doses (28.0, 14.0, and 7.0 mg/kg) (59)Fe-CPIC in SD rats. The pharmacokinetic parameters was obtained using DAS 2.0 program for analysis of tissue distribution and elimination of (59)Fe-CPIC.

RESULTSThe standard curve was linear within the range of 0.14-141 µg/ml (r=0.9999, n=5). The average recovery was 95% with a relative standard deviation no more than 15%. The pharmacokinetic parameters at 3 doses obtained, namely t1/2 and AUC (0-), were 214∓104, 231∓110, and 181∓81 min, and 1986.3∓513.3, 737.0∓467.0, and 315.1∓226.1 mg·min-1·L(-)1, respectively. (59)Fe-CPIC were detected in all the 13 tissues types examined and high radioactivity intensity was found in the gastrointestinal tract, hematogenic organs and other organs rich in blood. (59)Fe-CPIC was eliminated after intragastric administration primarily via the feces in rats.

CONCLUSIONThe method we established is easy and specific, and the pharmacokinetic parameters of (59)Fe-CPIC fit the two- compartment open model.

Administration, Oral ; Animals ; Area Under Curve ; Coordination Complexes ; administration & dosage ; pharmacokinetics ; urine ; Feces ; chemistry ; Female ; Intestinal Absorption ; Iron ; administration & dosage ; pharmacokinetics ; urine ; Iron Radioisotopes ; Male ; Polysaccharides ; administration & dosage ; isolation & purification ; pharmacokinetics ; urine ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tissue Distribution ; Zea mays ; chemistry

Radioiodine is a routine therapy for differentiated thyroid cancers. Non-thyroid cancers can intake radioiodine after transfection of the human sodium iodide symporter (hNIS) gene. The human telomerase reverse transcriptase (hTERT) promoter, an excellent tumor-specific promoter, has potential value for targeted gene therapy of glioma. We used the hTERT promoter to drive the expression of the hNIS and human thyroid peroxidase (hTPO) gene as a primary step for testing the effects of radioiodine therapy on malignant glioma. The U87 and U251 cells were co-transfected with two adenoviral vectors, in which the hNIS gene had been coupled to the hTERT promoter and the hTPO gene had been coupled to the CMV promoter, respectively. Then, we performed Western blot, 125I intake and efflux assays, and clonogenic assay with cancer cells. We also did 99mTc tumor imaging of nude mice models. After co-transfection with Ad-hTERT-hNIS and Ad-CMV-hTPO, glioma cells showed the 125I intake almost 1.5 times higher than cells transfected with Ad-hTERT-hNIS alone. Western blots revealed bands of approximately 70 kDa and 110 kDa, consistent with the hNIS and hTPO proteins. In clonogenic assay, approximately 90% of co-transfected cells were killed, compared to 50% of control cells after incubated with 37 MBq of 131I. These results demonstrated that radioiodine therapy was effective in treating malignant glioma cell lines following induction of tumor-specific iodide intake by the hTERT promoter-directed hNIS expression in vitro. Co-transfected hNIS and hTPO genes can result in increased intake and longer retention of radioiodine. Nude mice harboring xenografts transfected with Ad-hTERT-NIS can take 99mTc scans.
Adenoviridae ; genetics ; Animals ; Autoantigens ; genetics ; metabolism ; Cell Line, Tumor ; Cell Survival ; Cytomegalovirus ; genetics ; Genetic Vectors ; Glioma ; diagnostic imaging ; genetics ; metabolism ; pathology ; Half-Life ; Humans ; Iodide Peroxidase ; genetics ; metabolism ; Iodine Radioisotopes ; metabolism ; Iron-Binding Proteins ; genetics ; metabolism ; Mice ; Mice, Nude ; Promoter Regions, Genetic ; Recombinant Proteins ; genetics ; metabolism ; Symporters ; genetics ; metabolism ; Technetium ; Telomerase ; genetics ; Tomography, Emission-Computed, Single-Photon ; Transfection