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1.  Positron emission tomography imaging of CD105 expression in a rat myocardial infarction model with 64Cu-NOTA-TRC105 
Biological changes following myocardial infarction (MI) lead to increased secretion of angiogenic factors that subsequently stimulate the formation of new blood vessels as a compensatory mechanism to reverse ischemia. The goal of this study was to assess the role of CD105 expression during MI-induced angiogenesis by positron emission tomography (PET) imaging using 64Cu-labeled TRC105, an anti-CD105 monoclonal antibody. MI was induced by ligation of the left anterior descending (LAD) artery in female rats. Echocardiography and 18F-fluoro-2-deoxy-D-glucose (18F-FDG) PET scans were performed on post-operative day 3 to confirm the presence of MI in the infarct group and intact heart in the sham group, respectively. Ischemia-induced angiogenesis was non-invasively monitored with 64Cu-NOTA-TRC105 (an extensively validated PET tracer in our previous studies) PET on post-operative days 3, 10, and 17. Tracer uptake in the infarct zone was highest on day 3 following MI, which was significantly higher than that in the sham group (1.41 ± 0.45 %ID/g vs 0.57 ± 0.07 %ID/g; n=3, p<0.05). Subsequently, tracer uptake in the infarct zone decreased over time to the background level on day 17, whereas tracer uptake in the heart of sham rats remained low at all time points examined. Histopathology documented increased CD105 expression following MI, which corroborated in vivo findings. This study indicated that PET imaging of CD105 can be a useful tool for MI-related research, which can potentially improve MI patient management in the future upon clinical translation of the optimized PET tracers.
PMCID: PMC3867724  PMID: 24380040
Angiogenesis; myocardial infarction (MI); positron emission tomography (PET); CD105 (endoglin); molecular imaging; 64Cu
3.  Molecular MRI of VEGFR-2 reveals intra-tumor and inter-tumor heterogeneity 
Non-invasive and quantitative imaging of vascular endothelial growth factor receptor-2 (VEGFR-2) expression levels is highly important in cancer diagnosis, prognosis, and patient management. Although various literature reports have investigated the tumor expression levels of VEGFR-2 using imaging techniques such as positron emission tomography, single-photon emission computed tomography, targeted ultrasound, etc., accurate evaluation of the dynamic microdistribution of VEGFR-2 in vivo with good spatial and temporal resolution remains a major challenge. In this issue of the American Journal of Nuclear Medicine and Molecular Imaging, He at al. reported the use of a VEGFR-2 targeted probe for magnetic resonance imaging (MRI) of VEGFR-2 in two glioma models in rats (i.e. C6 and RG2). The heterogeneity of VEGFR-2 expression was non-invasively imaged with MRI and validated with various in vitro, in vivo, and ex vivo experiments. Not only was heterogeneous expression of VEGFR-2 found in different glioma tumors, it was also observed in different regions within the same tumor (e.g. tumor periphery, peri-necrotic area, and tumor interior). This report highlights the complex nature of gliomas, which may offer invaluable insights into tumor heterogeneity and potential clinical management of glioma patients. These patients have dismal clinical outcomes and are in urgent need of better tools to improve brain tumor treatment.
PMCID: PMC3715775  PMID: 23900733
Molecular MRI (mMRI); glioma; tumor angiogenesis; VEGFR-2; molecular imaging
5.  Molecular imaging of insulin-like growth factor 1 receptor in cancer 
Insulin-like growth factor 1 receptor (IGF1R) plays an important role in proliferation, apoptosis, angiogenesis, and tumor invasion. Histology and in situ hybridization studies have revealed that IGF1R was significantly up-regulated at the protein and mRNA level in many types of cancer. Since measuring IGF1R expression with immunohistochemistry has many limitations, non-invasive imaging of IGF1R can allow for more accurate patient stratification (e.g. selecting the right patient population for IGF1R-targeted therapy) and more effective monitoring of the therapeutic responses in cancer patients. In this review, we will summarize the current status of imaging IGF1R expression in cancer, which includes single-photon emission computed tomography, positron emission tomography, fluorescence, and γ-camera imaging. The four major classes of ligands that have been developed for non-invasive visualization of IGF1R will be discussed: proteins, antibodies, peptides, and affibodies. To date, molecular imaging of IGF1R expression is understudied and more research effort is needed in the future.
PMCID: PMC3468949  PMID: 23066521
Insulin-like growth factor 1 receptor (IGF1R); molecular imaging; peptide nucleic acid (PNA); positron emission tomography (PET); single-photon emission computed tomography (SPECT); cancer
6.  In a “nutshell”: intrinsically radio-labeled quantum dots 
Quantum dots (QDs) have many intriguing properties suitable for biomedical imaging applications. The poor tissue penetration of optical imaging in general, including those using QDs, has motivated the development of various QD-based dual-modality imaging agents. In this issue of AJNMMI (http://www.ajnmmi.us), Sun et al. reported the synthesis and in vitro/in vivo characterization of intrinsically radio-labeled QDs (r-QDs), where 109Cd was incorporated into the core/shell of QDs of various compositions. These r-QDs emit in the near-infrared range, have long circulation half-life, are quite stable with low cytotoxicity, exhibit small size and low accumulation in the reticuloendothelial system, and can allow for accurate measurement of their biodistribution in mice. With these desirable features demonstrated in this study, future development and optimization will further enhance the biomedical potential of intrinsically radio-labeled QDs.
PMCID: PMC3477731  PMID: 23133808
Quantum-dots (QDs); nanoparticle; positron emission tomography (PET); single-photon emission computed tomography (SPECT); near-infrared (NIR); optical imaging
7.  Molecular imaging of insulin-like growth factor 1 receptor in cancer 
Insulin-like growth factor 1 receptor (IGF1R) plays an important role in proliferation, apoptosis, angiogenesis, and tumor invasion. Histology and in situ hybridization studies have revealed that IGF1R was significantly up-regulated at the protein and mRNA level in many types of cancer. Since measuring IGF1R expression with immunohistochemistry has many limitations, non-invasive imaging of IGF1R can allow for more accurate patient stratification (e.g. selecting the right patient population for IGF1R-targeted therapy) and more effective monitoring of the therapeutic responses in cancer patients. In this review, we will summarize the current status of imaging IGF1R expression in cancer, which includes single-photon emission computed tomography, positron emission tomography, fluorescence, and γ-camera imaging. The four major classes of ligands that have been developed for non-invasive visualization of IGF1R will be discussed: proteins, antibodies, peptides, and affibodies. To date, molecular imaging of IGF1R expression is understudied and more research effort is needed in the future.
PMCID: PMC3477732  PMID: 23066521
Insulin-like growth factor 1 receptor (IGF1R); molecular imaging; peptide nucleic acid (PNA); positron emission tomography (PET); single-photon emission computed tomography (SPECT); cancer
8.  Positron emission tomography and near-infrared fluorescence imaging of vascular endothelial growth factor with dual-labeled bevacizumab 
The pivotal role of vascular endothelial growth factor (VEGF) in cancer is underscored by the approval of bevacizumab (Bev, a humanized anti-VEGF monoclonal antibody) for first line treatment of cancer patients. The aim of this study was to develop a dual-labeled Bev for both positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging of VEGF. Bev was conjugated to a NIRF dye (i.e. 800CW) and 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) before 64Cu-labeling. Flow cytometry analysis of U87MG human glioblastoma cells revealed no difference in VEGF binding affinity/specificity between Bev and NOTA-Bev-800CW. 64Cu-labeling of NOTA-Bev-800CW was achieved with high yield. Serial PET imaging of U87MG tumor-bearing female nude mice revealed that tumor uptake of 64Cu-NOTA-Bev-800CW was 4.6 ± 0.7, 16.3 ± 1.6, 18.1 ± 1.4 and 20.7 ± 3.7 %ID/g at 4, 24, 48 and 72 h post-injection respectively (n = 4), corroborated by in vivo/ex vivo NIRF imaging and biodistribution studies. Tumor uptake as measured by ex vivo NIRF imaging had a good linear correlation with the % ID/g values obtained from PET (R2 = 0.93). Blocking experiments and histology both confirmed the VEGF specificity of 64Cu-NOTA-Bev-800CW. The persistent, prominent, and VEGF-specific uptake of 64Cu-NOTA-Bev-800CW in the tumor, observed by both PET and NIRF imaging, warrants further investigation and future clinical translation of such Bev-based imaging agents.
PMCID: PMC3249831  PMID: 22229128
Positron emission tomography (PET); Near-infrared fluorescence (NIRF) Imaging; Vascular endothelial growth factor (VEGF); 64Cu; Tumor angiogenesis; Cancer
9.  Peptoid and positron emission tomography: an appealing combination 
Non-invasive and quantitative imaging of tumor angiogenesis is essential for lesion detection, patient stratification, drug development, and personalized anti-cancer therapies. In particular, the right timing is critical for antiangiogenic cancer therapy and non-invasive imaging can help determine whether to start and when to start such treatment. In this inaugural issue of the American Journal of Nuclear Medicine and Molecular Imaging, a peptoid-based positron emission tomography (PET) tracer was reported for imaging of VEGFR expression in a prostate cancer model. This important proof-of-principle study opened the door to a fertile area of research, which holds tremendous potential for various applications in future personalized medicine.
PMCID: PMC3183479  PMID: 22022661
Peptoid; cancer; tumor angiogenesis; positron emission tomography (PET); molecular imaging; 64Cu
12.  Imaging of induced pluripotent stem cells: from cellular reprogramming to transplantation 
Successful reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) ushered in a new era of regenerative medicine. Human iPSCs provide powerful new approaches for disease modeling, drug testing, developmental studies, and therapeutic applications. Investigating iPSC behavior in vivo and the ultimate feasibility of cell transplantation therapy necessitates the development of novel imaging techniques to longitudinally monitor iPSC localization, proliferation, integration, and differentiation in living subjects. At this five year mark of initial iPSC discovery, we review the current status of imaging iPSCs which ranges from in vitro studies, where imaging was used to study the processes/mechanisms of cellular reprogramming, to in vivo imaging of the survival of transplanted cells. To date, most imaging studies of iPSCs have been based on optical techniques, which include fluorescence and bioluminescence imaging. Since each imaging technique has its advantages and limitations, a combination of multiple imaging modalities may provide complementary information. The ideal imaging approach for tracking iPSCs or their derivatives in patients requires the imaging tag to be non-toxic, biocompatible, and highly specific to reduce perturbation of these cells. In few other scenarios can “personalized medicine” be better illustrated than the use of individual patient-specific iPSCs. Much future effort will be required before this can become a reality and clinical routine, where imaging will play an indispensible role in many facets of iPSC-based research and therapies.
PMCID: PMC3155258  PMID: 21841970
Induced pluripotent stem cells (iPSCs); molecular imaging; regenerative medicine; cell tracking; bioluminescence imaging (BLI); fluorescence imaging; positron emission tomography (PET); teratoma
13.  Positron Emission Tomography and Near-Infrared Fluorescence Imaging of Vascular Endothelial Growth Factor with Dual-Labeled Bevacizumab 
The pivotal role of vascular endothelial growth factor (VEGF) in cancer is underscored by the approval of bevacizumab (Bev, a humanized anti-VEGF monoclonal antibody) for first line treatment of cancer patients. The aim of this study was to develop a dual-labeled Bev for both positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging of VEGF. Bev was conjugated to a NIRF dye (i.e. 800CW) and 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) before 64Cu-labeling. Flow cytometry analysis of U87MG human glioblastoma cells revealed no difference in VEGF binding affinity/specificity between Bev and NOTA-Bev-800CW. 64Cu-labeling of NOTA-Bev-800CW was achieved with high yield. Serial PET imaging of U87MG tumor-bearing female nude mice revealed that tumor uptake of 64Cu-NOTA-Bev-800CW was 4.6 ± 0.7, 16.3 ± 1.6, 18.1 ± 1.4 and 20.7 ± 3.7 %ID/g at 4, 24, 48 and 72 h post-injection respectively (n = 4), corroborated by in vivo/ex vivo NIRF imaging and biodistribution studies. Tumor uptake as measured by ex vivo NIRF imaging had a good linear correlation with the %ID/g values obtained from PET (R2 = 0.93). Blocking experiments and histology both confirmed the VEGF specificity of 64Cu-NOTA-Bev-800CW. The persistent, prominent, and VEGF-specific uptake of 64Cu-NOTA-Bev-800CW in the tumor, observed by both PET and NIRF imaging, warrants further investigation and future clinical translation of such Bev-based imaging agents.
PMCID: PMC3249831  PMID: 22229128
Positron emission tomography (PET); Near-infrared fluorescence (NIRF) Imaging; Vascular endothelial growth factor (VEGF); 64Cu; Tumor angiogenesis; Cancer
14.  Peptoid and Positron Emission Tomography: an Appealing Combination 
Non-invasive and quantitative imaging of tumor angiogenesis is essential for lesion detection, patient stratification, drug development, and personalized anti-cancer therapies. In particular, the right timing is critical for anti-angiogenic cancer therapy and non-invasive imaging can help determine whether to start and when to start such treatment. In this inaugural issue of the American Journal of Nuclear Medicine and Molecular Imaging, a peptoid-based positron emission tomography (PET) tracer was reported for imaging of VEGFR expression in a prostate cancer model. This important proof-of-principle study opened the door to a fertile area of research, which holds tremendous potential for various applications in future personalized medicine.
PMCID: PMC3183479  PMID: 22022661
Peptoid; cancer; tumor angiogenesis; positron emission tomography (PET); molecular imaging; 64Cu
15.  Imaging of Induced Pluripotent Stem Cells: From Cellular Reprogramming to Transplantation 
Successful reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) ushered in a new era of regenerative medicine. Human iPSCs provide powerful new approaches for disease modeling, drug testing, developmental studies, and therapeutic applications. Investigating iPSC behavior in vivo and the ultimate feasibility of cell transplantation therapy necessitates the development of novel imaging techniques to longitudinally monitor iPSC localization, proliferation, integration, and differentiation in living subjects. At this five year mark of initial iPSC discovery, we review the current status of imaging iPSCs which ranges from in vitro studies, where imaging was used to study the processes/mechanisms of cellular reprogramming, to in vivo imaging of the survival of transplanted cells. To date, most imaging studies of iPSCs have been based on optical techniques, which include fluorescence and bioluminescence imaging. Since each imaging technique has its advantages and limitations, a combination of multiple imaging modalities may provide complementary information. The ideal imaging approach for tracking iPSCs or their derivatives in patients requires the imaging tag to be non-toxic, biocompatible, and highly specific to reduce perturbation of these cells. In few other scenarios can “personalized medicine” be better illustrated than the use of individual patient-specific iPSCs. Much future effort will be required before this can become a reality and clinical routine, where imaging will play an indispensible role in many facets of iPSC-based research and therapies.
PMCID: PMC3155258  PMID: 21841970
Induced pluripotent stem cells (iPSCs); molecular imaging; regenerative medicine; cell tracking; bioluminescence imaging (BLI); fluorescence imaging; positron emission tomography (PET); teratoma

Results 1-15 (15)