PT  - JOURNAL ARTICLE
AU  - Hong, Hao
AU  - Wang, Fei
AU  - Zhang, Yin
AU  - Barnhart, Todd
AU  - Theuer, Charles
AU  - Wang, Xudong
AU  - Cai, Weibo
TI  - Red fluorescent ZnO nanoparticle as a novel platform for cancer targeting and imaging
DP  - 2013 May 01
TA  - Journal of Nuclear Medicine
PG  - 439--439
VI  - 54
IP  - supplement 2
4099  - http://jnm.snmjournals.org/content/54/supplement_2/439.short
4100  - http://jnm.snmjournals.org/content/54/supplement_2/439.full
SO  - J Nucl Med2013 May 01; 54
AB  - 439 Objectives To employ intrinsically red fluorescent zinc oxide nanoparticles (ZnO NPs) for in vivo cancer targeting and imaging. Methods ZnO NPs were synthesized by thermal decomposition of Zn-organic coordination polymers, and conjugated to TRC105 (anti-CD105 antibody) and 1,4,7-triazacyclononane-N,N’N’’-triacetic acid (NOTA) through polyethylene glycol (PEG) linkers. SEM/TEM, dynamic light scattering, absorption/fluorescence spectra, and zeta-potential measurements were performed to characterize the as-synthesized and surface conjugated ZnO NPs. The intrinsic red fluorescence of ZnO NP facilitated microscopy studies, where CD105-positive HUVEC cells were incubated with NOTA-PEG-NP or NOTA-PEG-NP-TRC105. After 64Cu-labeling, positron emission tomography (PET) imaging, biodistribution, blocking, and histology studies were performed in 4T1 murine breast tumor-bearing mice to evaluate the tumor targeting capability of 64Cu-NOTA-PEG-NP-TRC105. 64Cu-NOTA-PEG-NP served as the control. Results Significant changes in zeta-potential and absorption spectra confirmed the success of PEG and TRC105 conjugation onto red fluorescent ZnO NPs (~60 nm) . Incubation with NOTA-PEG-NP-TRC105 resulted in greatly enhanced fluorescence signal on HUVECs compared to NOTA-PEG-NP. 64Cu-labeling was achieved with high yield and specific activity. Serial PET imaging revealed that 4T1 tumor uptake of 64Cu-NOTA-PEG-NP-TRC105 was 5.7±0.6, 6.4±0.8, and 6.8±0.2 %ID/g at 0.5, 3, and 16 h post-injection respectively (n=4), significantly higher than that of 64Cu-NOTA-PEG-NP (1.9±0.1, 2.5±0.2, and 2.4±0.4 %ID/g), which provided excellent tumor contrast and was corroborated by biodistribution studies. Blocking and histology experiments confirmed CD105 specificity of 64Cu-NOTA-PEG-NP-TRC105 in vivo. Conclusions We demonstrated for the first time that red fluorescent ZnO NPs can be used for fluorescence/PET imaging of cancer. With desirable properties such as biodegradability, versatile chemistry, and intrinsic fluorescence, ZnO NPs can serve as novel nanoplatforms for cancer imaging and therapy.