Open AccessJournal Article
Multimodality Molecular Imaging of Glioblastoma Growth Inhibition with Vasculature-Targeting Fusion Toxin VEGF121/rGel
Andrew R. Hsu,Weibo Cai,Anand Veeravagu,Khalid A. Mohamedali,Kai Chen,Sehoon Kim,Hannes Vogel,Lewis C. Hou,Victor Tse,Michael G. Rosenblum,Xiaoyuan Chen +10 more
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TLDR
The results of this study suggest that future clinical multimodality imaging and therapy with VEGF(121)/rGel may provide an effective means to prospectively identify patients who will benefit from VEG fusions therapy and then stratify, personalize, and monitor treatment to obtain optimal survival outcomes.Abstract:
Vascular endothelial growth factor A (VEGF-A) and its receptors, Flt-1/FLT-1 (VEGFR-1) and Flk-1/KDR (VEGFR-2), are key regulators of tumor angiogenesis and tumor growth. The purpose of this study was to determine the antiangiogenic and antitumor efficacies of a vasculature-targeting fusion toxin (VEGF121/rGel) composed of the VEGF-A isoform VEGF121 linked with a G4S tether to recombinant plant toxin gelonin (rGel) in an orthotopic glioblastoma mouse model by use of noninvasive in vivo bioluminescence imaging (BLI), MRI, and PET. Methods: Tumor-bearing mice were randomized into 2 groups and balanced according to BLI and MRI signals. PET with 64Cu-1,4,7,10-tetraazacyclododedane-N,N′,N″,N‴-tetraacetic acid (DOTA)-VEGF121/rGel was performed before VEGF121/rGel treatment. 18F-Fluorothymidine (18F-FLT) scans were obtained before and after treatment to evaluate VEGF121/rGel therapeutic efficacy. In vivo results were confirmed with ex vivo histologic and immunohistochemical analyses. Results: Logarithmic transformation of peak BLI tumor signal intensity revealed a strong correlation with MRI tumor volume (r = 0.89, n = 14). PET with 64Cu-DOTA-VEGF121/rGel before treatment revealed a tumor accumulation (mean ± SD) of 11.8 ± 2.3 percentage injected dose per gram at 18 h after injection, and the receptor specificity of the tumor accumulation was confirmed by successful blocking of the uptake in the presence of an excess amount of VEGF121. PET with 18F-FLT revealed significant a decrease in tumor proliferation in VEGF121/rGel-treated mice compared with control mice. Histologic analysis revealed specific tumor neovasculature damage after treatment with 4 doses of VEGF121/rGel; this damage was accompanied by a significant decrease in peak BLI tumor signal intensity. Conclusion: The results of this study suggest that future clinical multimodality imaging and therapy with VEGF121/rGel may provide an effective means to prospectively identify patients who will benefit from VEGF121/rGel therapy and then stratify, personalize, and monitor treatment to obtain optimal survival outcomes.read more
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Coordinating Radiometals of Copper, Gallium, Indium, Yttrium and Zirconium for PET and SPECT Imaging of Disease
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Multimodality molecular imaging of tumor angiogenesis.
Weibo Cai,Xiaoyuan Chen +1 more
TL;DR: The current status of tumor angiogenesis imaging with SPECT, PET, molecular MRI, targeted ultrasound, and optical techniques is summarized and only nanoparticle-based probes, which truly target the tumor vasculature rather than tumor cells because of poor extravasation, are discussed.
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Are quantum dots ready for in vivo imaging in human subjects
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Classification and evaluation strategies of auto‐segmentation approaches for PET: Report of AAPM task group No. 211
Mathieu Hatt,John Aldo Lee,Charles Schmidtlein,Issam El Naqa,Curtis B. Caldwell,Elisabetta De Bernardi,Wei Lu,Shiva K. Das,Xavier Geets,Vincent Grégoire,Robert Jeraj,Michael MacManus,Osama Mawlawi,Ursula Nestle,Andrei Pugachev,Heiko Schöder,Tony Shepherd,Emiliano Spezi,Dimitris Visvikis,Habib Zaidi,Assen S. Kirov +20 more
TL;DR: An overview of the present state‐of‐the‐art PET auto‐segmentation (PET‐AS) algorithms and their respective validation is provided, with an emphasis on providing the user with help in understanding the challenges and pitfalls associated with selecting and implementing a PET‐AS algorithm for a particular application.
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Bioluminescent imaging: a critical tool in pre-clinical oncology research.
Karen O'Neill,Scott K. Lyons,William M. Gallagher,Kathleen M. Curran,Annette T. Byrne,Annette T. Byrne +5 more
TL;DR: This review aims to provide insight into the principles of BLI and its applications in cancer research, and to highlight the versatility and potential of bioluminescent imaging in future oncological research.
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TL;DR: In this article, a single intravascular injection of a cyclic peptide or monoclonal antibody antagonist of integrin alpha v beta 3 disrupts ongoing angiogenesis on the chick chorioallantoic membrane (CAM).
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Vascular permeability factor (VPF, VEGF) in tumor biology
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TL;DR: VPF/VEGF has recently been found to have a role in wound healing and its expression by activated macrophages suggests that it probably also participates in certain types of chronic inflammation.
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Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in breast cancer
Lawrence F. Brown,Brygida Berse,Robert W. Jackman,Kathi Tognazzi,Anthony J. Guidi,Harold F. Dvorak,Donald R. Senger,James L. Connolly,Stuart J. Schnitt +8 more
TL;DR: The intense expression of VPF mRNA by breast carcinoma cells and ofVPF receptor mRNA by endothelial cells of adjacent small blood vessels provides strong evidence linking VPF expression to the angiogenesis associated with comedo-type DCIS, infiltrating ductal, and metastatic ductal breast carcinomas.
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Validation of FLT uptake as a measure of thymidine kinase-1 activity in A549 carcinoma cells
TL;DR: Results suggest that FLT images reflect TK(1) activity and the percentage of cells in S phase, and suggest that inhibition of cell cycle progression prevents FLT uptake and increased TK-1 activity.
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Selective Inhibition of Vascular Endothelial Growth Factor (VEGF) Receptor 2 (KDR/Flk-1) Activity by a Monoclonal Anti-VEGF Antibody Blocks Tumor Growth in Mice
Rolf A. Brekken,Jay P. Overholser,Victor Stastny,Johannes Waltenberger,John D. Minna,Philip E. Thorpe +5 more
TL;DR: 2C3 has potent antitumor activity, inhibiting the growth of newly injected and established human tumor xenografts in mice and highlighting the dominant role of VEGFR2 in mediating VEGF-induced vascular permeability increase and tumor angiogenesis.