Targeting Acidity in Pancreatic Adenocarcinoma: Multispectral Optoacoustic Tomography Detects pH-low Insertion Peptide Probes in vivo

作者: Charles W Kimbrough , Anil Khanal , Matthew Zeiderman , Bigya R Khanal , Neal C Burton

DOI: 10.1158/1078-0432.CCR-15-0314

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摘要: Background: pH-low Insertion Peptides (pHLIPs) can serve as a targeting moiety that enables pH-sensitive probes to detect solid tumors. Using these in conjunction with multispectral optoacoustic tomography (MSOT) is promising approach improve imaging for pancreatic cancer. Methods: A pHLIP (V7) was conjugated 750 NIR fluorescent dye and evaluated targeted probe adenocarcinoma. The pH-insensitive K7 served an untargeted control. Probe binding assessed vitro at pH 7.4, 6.8, 6.6 using human cell lines S2VP10 S2013. MSOT, semi-quantitative accumulation then vivo murine orthotopic adenocarcinoma model. Results: In vitro, the V7-750 demonstrated significantly higher fluorescence compared 7.4 (S2VP10, p=0.0119; S2013, p=0.0160), while no difference observed K7-750 control p=0.8783; p=0.921). model, resulted 782.5 MSOT a.u. signal 5.3 tumor (p= 0.0001). Similarly, 578.3 S2013 model 5.1 (p=0.0005). There minimal off-target of within liver or kidney, distribution confirmed ex imaging. Conclusion: Compared controls, specifically targets adenocarcinoma, has accumulation. non-invasive detection pH-targeted by means represents modality monitoring

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