RT Journal Article
SR Electronic
T1 Red fluorescent ZnO nanoparticle as a novel platform for cancer targeting and imaging
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 439
OP 439
VO 54
IS supplement 2
A1 Hong, Hao
A1 Wang, Fei
A1 Zhang, Yin
A1 Barnhart, Todd
A1 Theuer, Charles
A1 Wang, Xudong
A1 Cai, Weibo
YR 2013
UL http://jnm.snmjournals.org/content/54/supplement_2/439.abstract
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.