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Wu M.,CAS Technical Institute of Physics and Chemistry | Shi J.,Medical Isotopes Research Center | Shi J.,Peking University | Fan D.,Medical Isotopes Research Center | And 4 more authors.
Biomacromolecules | Year: 2013

Viral nanoparticles (VNPs) have shown great potential as platforms for biomedical applications. Before using VNPs for further biomedical applications, it is important to clarify their biological behavior in vivo, which is rare for rod-like VNPs. In this paper, a study of tobacco mosaic virus (TMV), a typical rod-like VNP, is performed on blood clearance kinetics, biodistributions in both normal and tumor-bearing mice, histopathology and cytotoxicity. TMV was radiolabeled with 125I using Iodogen method for in vivo quantitative analysis and imaging purpose. In the normal mice, the accumulation of TMV in the immune system led to a rapid blood clearance. The uptake of TMVs in the liver was less than that in the spleen, which is opposite to the results observed in the case of spherical VNPs. No signs of overt toxicity were observed in examined tissues according to the results of histological analysis. In addition, similar biodistribution patterns were observed in U87MG tumor-bearing mice. © 2013 American Chemical Society.


Fan D.,Medical Isotopes Research Center | Zhang X.,Medical Isotopes Research Center | Zhong L.,Peking University | Liu X.,Medical Isotopes Research Center | And 11 more authors.
Bioconjugate Chemistry | Year: 2015

β-Emitters can produce Cerenkov radiation that is detectable by Cerenkov luminescence imaging (CLI), allowing the combination of PET and CLI with one radiotracer for both tumor diagnosis and visual guidance during surgery. Recently, the clinical feasibility of CLI with the established therapeutic reagent Na131I and the PET tracer 18F-FDG was demonstrated. 68Ga possesses a higher Cerenkov light output than 18F and 131I, which would result in higher sensitivity for CLI and improve the outcome of CLI in clinical applications. However, the research on 68Ga-based tumor-specific tracers for CLI is limited. In this study, we examined the use of 68Ga-radiolabeled DOTA-3PRGD2 (68Ga-3PRGD2) for dual PET and CLI of orthotopic U87MG human glioblastoma. For this purpose, the Cerenkov efficiencies of 68Ga and 18F were measured with the IVIS Spectrum system (PerkinElmer, USA). The CLI signal intensity of 68Ga was 15 times stronger than that of 18F. PET and CLI of 68Ga-3PRGD2 were performed in U87MG human glioblastoma xenografts. Both PET and CLI revealed a remarkable accumulation of 68Ga-3PRGD2 in the U87MG human glioblastoma xenografts at 1 h p.i. with an extremely low background in the brain when compared with 18F-FDG. Furthermore, 68Ga-3PRGD2 was used for dual PET and CLI of orthotopic human glioblastoma. The orthotopic human glioblastoma was clearly visualized by both imaging modalities. In addition, the biodistribution of 68Ga-3PRGD2 was assessed in normal mice to estimate the radiation dosimetry. The whole-body effective dose is 20.1 ± 3.3 μSv/MBq, which is equal to 3.7 mSv per whole-body PET scan with a 5 mCi injection dose. Thus, 68Ga-3PRGD2 involves less radiation exposure in patients when compared with 18F-FDG (7.0 mSv). The use of 68Ga-3PRGD2 in dual PET and CLI shows great promise for tumor diagnosis and image-guided surgery. © 2015 American Chemical Society.


Shi J.,Medical Isotopes Research Center | Shi J.,Peking Union Medical College | Cui L.,Medical Isotopes Research Center | Cui L.,Peking Union Medical College | And 16 more authors.
Molecular Imaging | Year: 2013

There is a critical need to develop diagnostic procedures enabling early detection of tumors while at a curable stage. Technetium 99m ( 99mTc)-labeled VQ peptide (99mTc-HYNIC-VQ) identified through screening phage display peptide libraries against fresh human colonic adenomas was prepared and evaluated for tumor detection. 99mTc-HYNIC- VQ was prepared by a non-SnCl2 method with more than 99% radiochemical purity. The biodistribution in the HT-29 tumor model showed that although the absolute tumor uptake values were relatively low (0.60 ± 0.09, 0.41 ± 0.09, 0.36 ± 0.18, and 0.19 ± 0.08 %ID/g at 0.5, 1, 2, and 4 hours postinjection, respectively), the tumor uptake was higher than that of any of the other organs except for the kidneys at any time point examined, which led to the high tumor to nontarget ratios. The tumors and inflammation were clearly visualized with high contrast. Although the mechanism of accumulation of radiolabeled VQ peptide in tumors and inflammation needs to be further investigated, 99mTc-HYNIC-VQ is a promising imaging agent for the early detection of tumors or premalignancies, at least for screening patients with a high risk of developing cancers. © 2013 Decker Publishing.

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