99m Tc-glycopeptide: synthesis, biodistribution and imaging in breast tumor-bearing rodents.
This study was aimed to develop a glycopeptide (GP) to be used as a carrier for anti-cancer drug delivery. GP was synthesized by conjugating glutamate peptide and chitosan using carbodiimide as a coupling agent. Elemental analysis and capillary electrophoresis confirmed the purity was >95%. GP was labeled with sodium pertechnetate (Na99m TcO4) for in vitro and in vivo studies. Rhenium-GP was synthesized to support the binding site of 99m Tc at the glutamate positions 3-5. In vitro cellular uptake of 99m Tc-GP was performed in breast cancer cells. Cytosol had 60% whereas nucleus had 40% uptake of 99m Tc-GP. When cancer cells were incubated with glutamate or aspartate, followed by 99m Tc-GP, there was decreased uptake in cells treated with glutamate but not aspartate. The findings indicated that cellular uptake of 99m Tc-GP was via glutamate transporters. In addition, 99m Tc-GP was able to measure uptake differences after cells treated with paclitaxel. Biodistribution and planar imaging were conducted in breast tumor-bearing rats. Biodistribution of 99m Tc-GP showed increased tumor-to-tissue ratios as a function of time. Planar images confirmed that 99m Tc-GP could assess tumor uptake changes after paclitaxel treatment. In vitro and in vivo studies indicated that GP could target tumor cells, thus, GP may be a useful carrier for anti-cancer drug delivery.
Center for Innovation Development, Taiwan Hopax Chems Mfg. Co., Ltd., No. 28, Hua Dong Road, Daliao, Kaohsiung 83162, Taiwan.
I-Chien
IC
Wei
Ning
N
Tsao
Ya-Hui
YH
Huang
Yen-Sheng
YS
Ho
Chung-Chin
CC
Wu
Dong-Fang
DF
Yu
David J
DJ
Yang
D000818:Animals; D019540:Area Under Curve; D045744:Cell Line, Tumor; D005260:Female; D006020:Glycopeptides / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D007553:Isotope Labeling; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D012588:Scintillation Counting; D014018:Tissue Distribution
D006020:Glycopeptides; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals