Pharmaceutical Research

, Volume 27, Issue 5, pp 933–942

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

Authors

  • Bing Gu
    • School of PharmacyFudan University
  • Cao Xie
    • School of PharmacyFudan University
  • Jianhua Zhu
    • School of PharmacyFudan University
  • Wei He
    • Department of Nuclear MedicineHuadong Hospital
    • School of PharmacyFudan University
Research Paper

DOI: 10.1007/s11095-010-0100-3

Cite this article as:
Gu, B., Xie, C., Zhu, J. et al. Pharm Res (2010) 27: 933. doi:10.1007/s11095-010-0100-3

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.

KEY WORDS

fluorescent imagingfolate-PEG-CKK2-DTPAlymph targetingradio active tracingtumor targeting

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

Copyright information

© Springer Science+Business Media, LLC 2010