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Folate-PEG-CKK2-DTPA, A Potential Carrier for Lymph-Metastasized Tumor Targeting

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ABSTRACT

Purpose

A novel conjugate, Folate-PEG-CKK2-DTPA, was designed and prepared as a carrier for lymphatic metastasized tumor imaging diagnosis and targeting therapy.

Methods

Folate-PEG-CKK2-DTPA was synthesized and characterized by analysis High Performance Liquid Chromatography, Size Exclusive Chromatography and 1H-NMR. 99mTc-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-CKK2-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-CKK2-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-CKK2-DTPA as a novel and dependable carrier for tumor diagnosis and therapy, especially for lymph-metastasized tumors.

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Abbreviations

BCS:

Bull Calf Serum

CKK2 :

cysteine-L-lysine-(L-lysine)2

DIPEA:

N,N-Diisopropylethylamine

DMSO:

dimethyl sulfoxide

DTPA:

diethylenetriaminepentaacetic acid

EDA:

Ethylenediamine

EDC·HCl:

1-Ethyl-3-(3-dimethyllaminopropyl) carbodiimide hydrochloride

FBS:

Fetal bovine serum

FITC:

Fluorescein-5-isothiocyanate

FR:

Folate receptor

HBTU:

O-Benzotriazole-N,N,N′,N′-tetramethyl-uronium-hexafluorophosphate

HF:

hydrogen fluoride

HOBT:

Hydroxybenzotriazole

HPLC:

high-performance liquid chromatography

KB:

human oral epidermoid carcinoma

Mal-PEG-NHS:

maleimide-polyethyl glycol-succinimidyl ester

ROI:

Region of Interest

SPECT:

Single-Photon-Emission Computed Tomography

TFA:

trifluoacetic acid

1H NMR:

1H nuclear magnetic resonance

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ACKNOWLEDGEMENTS

This work was supported by National Science and Technology Major Project of China (2009ZX09310-006), National Basic Research Program of China (973 Program, 2010CB934000) and National High-Tech Research & Development Program of China (863 program, 2006AA03Z325).

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Authors and Affiliations

  1. School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China

    Bing Gu, Cao Xie, Jianhua Zhu & Weiyue Lu

  2. Department of Nuclear Medicine, Huadong Hospital, Shanghai, 200040, China

    Wei He

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  1. Bing Gu
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  2. Cao Xie
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Correspondence to Weiyue Lu.

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Gu, B., Xie, C., Zhu, J. et al. Folate-PEG-CKK2-DTPA, A Potential Carrier for Lymph-Metastasized Tumor Targeting. Pharm Res 27, 933–942 (2010). https://doi.org/10.1007/s11095-010-0100-3

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  • DOI: https://doi.org/10.1007/s11095-010-0100-3

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