PT  - JOURNAL ARTICLE
AU  - Chen, Feng
AU  - Nayak, Tapas
AU  - Hong, Hao
AU  - Graves, Stephen
AU  - Nickles, Robert
AU  - Cai, Weibo
TI  - In vivo tumor targeting with dual-labeled mesoporous silica nanoparticles
DP  - 2014 May 01
TA  - Journal of Nuclear Medicine
PG  - 58--58
VI  - 55
IP  - supplement 1
4099  - http://jnm.snmjournals.org/content/55/supplement_1/58.short
4100  - http://jnm.snmjournals.org/content/55/supplement_1/58.full
SO  - J Nucl Med2014 May 01; 55
AB  - 58 Objectives To develop novel multifunctional mesoporous silica nanoparticles (MSN) for in vivo tumor targeting, and to track them with PET and near-infrared fluorescence (NIRF) imaging. Methods Fab fragment of TRC105 (an antibody that binds to CD105, overexpressed on tumor neovasculature) was generated by enzymatic papain digestion. Uniform ~80 nm sized MSNs were synthesized via a soft-template method, and conjugated to 800CW (a NIRF dye), NOTA (a chelator for 64Cu labeling), polyethylene glycol (PEG) and TRC105(Fab) to form 64Cu-NOTA-MSN-800CW-PEG-TRC105(Fab). Similar conjugate without TRC105(Fab) was also made as non-targeted control. Systematic in vivo PET/NIRF imaging, biodistribution, and blocking studies were performed in 4T1 tumor-bearing mice (CD105+) to evaluate and confirm tumor targeting capability, validated by various in vitro/ex vivo studies. Results TRC105(Fab) was produced with high purity, confirmed by SDS-PAGE and HPLC. After confirmation of successful surface modifications of MSN to yield NOTA-MSN-800CW-PEG-TRC105(Fab), in vitro CD105 targeting studies in HUVEC (CD105+) and MCF-7 cells (CD105-) showed strong and specific binding of the conjugate to CD105, with negligible non-specific binding. NOTA-MSN-800CW-PEG-TRC105(Fab) was labeled with 64Cu with good yield and high purity (>95%). High stability of both 800CW and 64Cu in 64Cu-NOTA-MSN-800CW-PEG-TRC105(Fab) was confirmed by serum stability studies for 48 h. In vivo PET/NIRF imaging showed specific targeting of 64Cu-NOTA-MSN-800CW-PEG-TRC105(Fab) in 4T1 mice, with peak tumor uptake of 5.5±0.4 %ID/g at 0.5 h (n=3), ~ 2 fold higher than the non-targeted control. CD105 specificity of 64Cu-NOTA-MSN-800CW-PEG-TRC105(Fab) was confirmed by blocking and ex vivo histology studies. Conclusions This is the first example of tumor targeted dual-modality PET/NIRF imaging with functionalized MSN, which had ~2 fold higher tumor uptake than that of passive targeting alone. With high drug loading capability and good biocompatibility of MSN, this nanosystem is highly suitable for PET/NIRF image-guided drug delivery and targeted cancer therapy.