Folate-PEG-CKK(2)-DTPA, A Potential Carrier for Lymph-Metastasized Tumor Targeting.
OBJECTIVE
A novel conjugate, Folate-PEG-CKK(2)-DTPA, was designed and prepared as a carrier for lymphatic metastasized tumor imaging diagnosis and targeting therapy.


METHODS
Folate-PEG-CKK(2)-DTPA was synthesized and characterized by analysis High Performance Liquid Chromatography, Size Exclusive Chromatography and (1)H-NMR. (99m)Tc-labeled conjugation was prepared, and in vivo quantitative biodistribution and SPECT imaging were studied after subcutaneously injected into the rats and rabbits, respectively. Cell uptake study was carried in a KB cell line using fluorescent methods. In vivo and ex vivo fluorescent imaging study was carried in tumor-bearing nude mouse to evaluate its targeting ability.


RESULTS
Folate-PEG-CKK(2)-DTPA was synthesized with high purity. Both in vivo biodistribution study and SPECT imaging study show the rapid direction and high distribution of the conjugation to the lymph nodes. The uptake of fluorescence-labeled Folate-PEG-CKK(2)-DTPA in human oral epidermis carcinoma cells was observed. In vivo and ex vivo fluorescent imaging study indicated it could accumulate in tumor region after vein tail injection in nude mouse.


CONCLUSIONS
All these findings suggested Folate-PEG-CKK(2)-DTPA as a novel and dependable carrier for tumor diagnosis and therapy, especially for lymph-metastasized tumors.
Gu
Bing
B
School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China.
Xie
Cao
C
Zhu
Jianhua
J
He
Wei
W
Lu
Weiyue
W
D000818:Animals; D004337:Drug Carriers / Q000138:chemical synthesis*; D016503:Drug Delivery Systems; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D005492:Folic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D007553:Isotope Labeling; D007624:KB Cells; D008198:Lymph Nodes / Q000000981:diagnostic imaging; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000737:chemistry*; D004369:Pentetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D011092:Polyethylene Glycols / Q000737:chemistry*; D011817:Rabbits; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D016284:Technetium Tc 99m Pentetate / Q000008:administration & dosage / Q000737:chemistry*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
D004337:Drug Carriers; D005456:Fluorescent Dyes; D009842:Oligopeptides; D019275:Radiopharmaceuticals; D011092:Polyethylene Glycols; D004369:Pentetic Acid; D005492:Folic Acid; D016650:Fluorescein-5-isothiocyanate; D016284:Technetium Tc 99m Pentetate