Radiolabeling of SPION-dopa-PEG-DOTA/RGD With <sup>64</sup>Cu and Biodistribution of the Radiolabel

SHI Xu-dong; WANG Xiao; SHEN Yi-ming; SUN Yu-lin; LIANG Ji-xin; CHEN Yu-qing; SHEN Lang-tao

doi:10.7538/hhx.2015.37.04.0250

Journal of Nuclear and Radiochemistry > 2015 > 37(4): 250-256. > DOI: 10.7538/hhx.2015.37.04.0250

SHI Xu-dong, WANG Xiao, SHEN Yi-ming, SUN Yu-lin, LIANG Ji-xin, CHEN Yu-qing, SHEN Lang-tao. Radiolabeling of SPION-dopa-PEG-DOTA/RGD With ⁶⁴Cu and Biodistribution of the Radiolabel[J]. Journal of Nuclear and Radiochemistry, 2015, 37(4): 250-256. DOI: 10.7538/hhx.2015.37.04.0250

Citation:

PDF (901 KB)

Radiolabeling of SPION-dopa-PEG-DOTA/RGD With ⁶⁴Cu and Biodistribution of the Radiolabel

1.
China Institute of Atomic Energy, P. O. Box 275(58), Beijing 102413, China
2.
Atom High-Tech Co., Ltd, Beijing 102413, China

More Information

Graphical Abstract

Abstract

Abstract

To investigate the construction and purification of the superparamagnetic iron oxide nanoparticles radiolabeled with ⁶⁴Cu and its biodistribution in mice, ⁶⁴Cu-SPION-dopa-PEG-DOTA/RGD was prepared. To obtain a fair good radiolabeling yield and a high radiochemical purity, the labeling conditions and purification method for ⁶⁴Cu-SPION-dopa-PEG-DOTA/RGD were optimized．Besides, stability in vitro and biodistribution studies in mice for ⁶⁴Cu-SPION-dopa-PEG-DOTA/RGD were also studied．The labeling conditions were optimized and the radiolabeling yield is 63%. The radiochemical purity of ⁶⁴Cu-SPION-dopa-PEG-DOTA/RGD is more than 95% after purification. It is stable enough in the systems of PBS and HSA, respectively, within 12 h at room temperature. The octanol-water partition coefficients of ⁶⁴Cu-SPION-dopa-PEG-DOTA/RGD (lg P) is -1.27. ⁶⁴Cu-SPION-dopa-PEG-DOTA/RGD exhibites a relatively high uptake in liver and kindney and shows rapid clearance from blood based on the biodistribution studies．SPION-dopa-PEG-DOTA/RGD was radiolabeled with ⁶⁴Cu and purified successfully. ⁶⁴Cu-SPION-dopa-PEG-DOTA/RGD shows high stability in vitro. Biodistribution in vivo reveals the main metabolic pathway of this radiolabel, which can be further investigated acting as a PET/MRI dual modal imaging agent.
- ⁶⁴Cu,
- superparamagnetic iron oxide nanoparticles,
- radiochemical purity,
- stability in vitro,
- biodistribution

FullText(HTML)

References (17)

References

[1]	Reddy L H, Arias J L, Nicolas J, et al. Magnetic nanoparticles: design and characterization, toxicity and biocompatibility, pharmaceutical and biomedical applications[J]. Chem Rev, 2012, 112(11): 5818-5878.
[2]	Rafael T, Richard T, Philip J, et al. Synthesis of ⁶⁴CuⅡ-bis(dithiocarbamatebisphosphonate) and its conjugation with superparamagnetic iron oxide nanoparticles: in vivo evaluation as dual-modality PET-MRI agent[J]. Angew Chem Int Ed, 2011, 50(24): 5509-5513.
[3]	Xie J, Chen K, Huang J, et al. PET/NIRF/MRI triple functional iron oxide nanoparticles[J]. Biomaterials, 2010, 31(22): 3016-3022.
[4]	Choi J, Park J, Cheon J, et al. A hybrid nanoparticle probe for dual-modality positron emission tomography and magnetic resonance imaging[J]. Angew Chem Int Ed, 2008, 47(33): 6259-6262.
[5]	Shi X D, Shen L T. The design and synthesis of potential PET/MRI dual-modal imaging agents based on MFe₂O₄ (M=Fe, Mn) nanoparticles[J]. J Nucl Med, 2014, 55(Suppl.): 1026.
[6]	史旭东，沈浪涛.用于PET/MRI双模式显像剂的磁性氧化铁纳米粒子的合成和性质初步研究[G]∥中国原子能科学研究院年报.北京：中国原子能科学研究院，2012：179-180.
[7]	Panizzi P, Nahrendorf M, Weissleder R, et al. In vivo detection of staphylococcus aureus endocarditis by targeting pathogen-specific prothrombin activation[J]. Nat Med, 2011, 17(9): 1142-1146.
[8]	Joanne E M, James R B, David M C. Functional imaging of human epidermal growth factor receptor 2-positive metastatic breast cancer using ⁶⁴Cu-DOTA-trastuzumab PET[J]. J Nucl Med, 2014, 55(1):23-29.
[9]	Elena R, Réjean L, Brigitte G, et al. ⁶⁸Ga/DOTA and ⁶⁴Cu/NOTA-phthalocyanine conjugates as fluorescent/PET bimodal imaging probes[J]. Bioconjugate Chem, 2013, 24(9): 1624-1633.
[10]	Benjamin R, David L, Angelique Y. Synthesis of ⁶⁴Cu-labeled magnetic nanoparticles for multimodal imaging[J]. Bioconjugate Chem, 2008, 19(7): 1496-1504.
[11]	Yang M, Cheng K, Cheng Z, et al. Affibody modified and radiolabeled gold-iron oxide hetero-nanostructures for tumor PET, optical and MR imaging[J]. Biomaterials, 2013, 34(11): 2796-2806.
[12]	Lee H Y, Li Z B, Chen X Y, et al. PET/MRI dual modality tumor imaging using arginine glycine aspartic (RGD) conjugated radiolabeled iron oxide nanoparticles[J]. J Nucl Med, 2008, 49 (8): 1371-1379.
[13]	Fukukawa K, Rossin R, Hagooly A, et al. Synthesis and characterization of core-shell star copolymers for in vivo PET imaging applications[J].Biomacromolecules, 2008, 9(4): 1329-1339.
[14]	Pressly E D, Rossin R, Hagooly A, et al. Structural effects on the biodistribution and positron emission tomography(PET) imaging of well defined⁶⁴Cu-labeled nanoparticles comprised of amphiphilic block graft copolymers[J].Biomacromolecules, 2007, 8(10): 3126-3134.
[15]	Natarajan A, Gruettner C, Ivkov R, et al. Nanoferrite particle based radioimmuno nanoparticles: binding affinity and in vivo pharmacokinetics[J]. Bioconjugate Chem, 2008, 19(6): 1211-1218.
[16]	Glaus C, Rossin R, Bao G. In vivo evaluation of ⁶⁴Cu-labeled magnetic nanoparticles as a dual modality PET/MR imaging agent[J]. Bioconjugate Chem, 2010, 21(4): 715-722.
[17]	Laurent S, Forge D, Muller R. Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications[J]. Chem Rev, 2008, 108(6): 2064-2110.

Cited By

Get Citation

PDF

XML

Article views (1168) PDF downloads (4351)

Turn off MathJax

Article Contents

Abstract

References

Radiolabeling of SPION-dopa-PEG-DOTA/RGD With 64Cu and Biodistribution of the Radiolabel

Abstract

References

Catalog

Export File

Citation

Format

Content

Radiolabeling of SPION-dopa-PEG-DOTA/RGD With ⁶⁴Cu and Biodistribution of the Radiolabel