Molecular Imaging最新文献

The combination of different modality images can provide detailed and comprehensive information for the prognostic assessment and therapeutic strategy of patients with ischemic heart disease. In this study, a 3D fusion framework is designed to integrate coronary computed tomography (CT) angiography (CTA), 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]DG) positron emission tomography (PET)/CT, and [⁶⁸Ga]-1,4,7-triazacyclononane-1,4,7-triacetic acid-(Arg-Gly-Asp)2 ([⁶⁸Ga]-NOTA-PRGD2) PET/CT images of the myocardial infarction model in minipigs. First, the structural anatomy of the heart in coronary CTA and CT is segmented using a multi-atlas-based method. Then, the hearts are registered using the B-spline-based free form deformation. Finally, the [¹⁸F]DG and [⁶⁸Ga]-NOTA-PRGD2 signals are mapped into the heart in coronary CTA, which produces a single fusion image to delineate both the cardiac structural anatomy and the functional information of myocardial viability and angiogenesis. Heart segmentation demonstrates high accuracy with good agreement between manual delineation and automatic segmentation. The fusion result intuitively reflects the extent of the [¹⁸F]DG uptake defect as well as the location where the [⁶⁸Ga]-NOTA-PRGD2 signal appears. The fusion result verified the occurrence of angiogenesis based on the in vivo noninvasive molecular imaging approach. The presented framework is helpful in facilitating the study of the relationship between infarct territories and blocked coronary arteries as well as angiogenesis.

The value of combined L-( methyl-[¹¹C]) methionine positron-emitting tomography (MET-PET) and magnetic resonance imaging (MRI) with regard to tumor extent, entity prediction, and therapy effects in clinical routine in patients with suspicion of a brain tumor was investigated. In n = 65 patients with histologically verified brain lesions n = 70 MET-PET and MRI (T1-weighted gadolinium-enhanced [T1w-Gd] and fluid-attenuated inversion recovery or T2-weighted [FLAIR/T2w]) examinations were performed. The computer software "visualization and analysis framework volume rendering engine (Voreen)" was used for analysis of extent and intersection of tumor compartments. Binary logistic regression models were developed to differentiate between World Health Organization (WHO) tumor types/grades. Tumor sizes as defined by thresholding based on tumor-to-background ratios were significantly different as determined by MET-PET (21.6 ± 36.8 cm³), T1w-Gd-MRI (3.9 ± 7.8 cm³), and FLAIR/T2-MRI (64.8 ± 60.4 cm³; P < .001). The MET-PET visualized tumor activity where MRI parameters were negative: PET positive tumor volume without Gd enhancement was 19.8 ± 35.0 cm³ and without changes in FLAIR/T2 10.3 ± 25.7 cm³. FLAIR/T2-MRI visualized greatest tumor extent with differences to MET-PET being greater in posttherapy (64.6 ± 62.7 cm³) than in newly diagnosed patients (20.5 ± 52.6 cm³). The binary logistic regression model differentiated between WHO tumor types (fibrillary astrocytoma II n = 10 from other gliomas n = 16) with an accuracy of 80.8% in patients at primary diagnosis. Combined PET and MRI improve the evaluation of tumor activity, extent, type/grade prediction, and therapy-induced changes in patients with glioma and serve information highly relevant for diagnosis and management.

This report describes a multimodal whole-body 3'-deoxy-3'[(18)F]-fluorothymidine positron emission tomography (FLT-PET) and dual-energy computed tomography (DECT) method to identify leukemia distribution within the bone marrow environment (BME) and to develop disease- and/or BME-specific radiation strategies. A control participant and a newly diagnosed patient with acute myeloid leukemia prior to induction chemotherapy were scanned with FLT-PET and DECT. The red marrow (RM) and yellow marrow (YM) of the BME were segmented from DECT using a basis material decomposition method. Functional total marrow irradiation (fTMI) treatment planning simulations were performed combining FLT-PET and DECT imaging to differentially target irradiation to the leukemia niche and the rest of the skeleton. Leukemia colonized both RM and YM regions, adheres to the cortical bone in the spine, and has enhanced activity in the proximal/distal femur, suggesting a potential association of leukemia with the BME. The planning target volume was reduced significantly in fTMI compared with conventional TMI. The dose to active disease (standardized uptake value >4) was increased by 2-fold, while maintaining doses to critical organs similar to those in conventional TMI. In conclusion, a hybrid system of functional-anatomical-physiological imaging can identify the spatial distribution of leukemia and will be useful to both help understand the leukemia niche and develop targeted radiation strategies.

The aim of this study was to use a multimodal molecular imaging approach to serially assess regional metabolic changes in the knee in an in vivo anterior cruciate ligament transection (ACLT) canine model of osteoarthritis (OA). Five canine underwent ACLT in one knee and the contralateral knee served as uninjured control. Prior, 3, 6, and 12 weeks post-ACLT, the dogs underwent ¹⁸F-fluoro-d-glucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT) and magnetic resonance imaging (MRI). The MRI was coregistered with the PET/CT, and 3-dimensional regions of interest (ROIs) were traced manually and maximum standardized uptake values (SUV_max) were evaluated. ¹⁸F-fluoro-d-glucose SUV_max in the ACLT knee ROIs was significantly higher compared to the uninjured contralateral knees at 3, 6, and 12 weeks. Higher ¹⁸F-FDG uptake observed in ACLT knees compared to the uninjured knees reflects greater metabolic changes in the injured knees over time. Knee ¹⁸F-FDG uptake in an in vivo ACLT canine model using combined PET/CT and MRI demonstrated to be highly sensitive in the detection of metabolic alterations in osseous and nonosteochondral structures comprising the knee joint. ¹⁸F-fluoro-d-glucose appeared to be a capable potential imaging biomarker for early human knee OA diagnosis, prognosis, and management.

Strategies to enhance the relaxometric properties of gadolinium (Gd)-based contrast agents (CAs) for magnetic resonance imaging (MRI), without the chemical modification of chelates, have recently had a strong impact on the diagnostic field. We have taken advantage of the interaction between Gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA) and the hydrogel structure of hyaluronic acid to design cross-linked hyaluronic acid nanoparticles down to 35 nm for use in MRI applications. The proposed bioformulations enable the control of the relaxometric properties of CAs, thus boosting the relaxation rate of T1. Our results led us to identify this approach as an adjustable scenario to design intravascularly injectable hydrogel nanoparticles entrapping Gd-DTPA. This approach overcomes the general drawbacks of clinically approved CAs having poor relaxivity and toxic effects.

The important role of insulin-like growth factor 1 receptor (IGF-1R) in malignant tumors has been well established. Increased IGF-1R activity promotes cancer cell proliferation, migration, and invasion and is associated with tumor metastasis, treatment resistance, poor prognosis, and shortened survival in patients with cancer. However, while IGF-1R has become a promising target for cancer therapy, IGF-1R-targeted therapy is ineffective in unselected patients. It is therefore essential to evaluate IGF-1R expression before treatment in order to identify responsive patients, monitor therapy efficacy, and estimate prognosis. Insulin-like growth factor 1 receptor molecular imaging is an optimal method for assessing the expression of IGF-1R in vivo accurately and noninvasively. In this review, we will summarize the current status of IGF-1R molecular imaging in cancer, in which 5 major classes of ligands that have been developed for noninvasive IGF-1R molecular imaging will be discussed: natural ligands, monoclonal antibodies, antibody fragments, affibodies, and small molecules. For decades, IGF-1R molecular imaging is studied in full swing and more effort is needed in the future.

Phosphatidylserine (PS), the most abundant anionic phospholipid in cell membrane, is strictly confined to the inner leaflet in normal cells. However, this PS asymmetry is found disruptive in many tumor vascular endothelial cells. We discuss the underlying mechanisms for PS asymmetry maintenance in normal cells and its loss in tumor cells. The specificity of PS exposure in tumor vasculature but not normal blood vessels may establish it a useful biomarker for cancer molecular imaging. Indeed, utilizing PS-targeting antibodies, multiple imaging probes have been developed and multimodal imaging data have shown their high tumor-selective targeting in various cancers. There is a critical need for improved diagnosis and therapy for brain tumors. We have recently established PS-targeted nanoplatforms, aiming to enhance delivery of imaging contrast agents across the blood-brain barrier to facilitate imaging of brain tumors. Advantages of using the nanodelivery system, in particular, lipid-based nanocarriers, are discussed here. We also describe our recent research interest in developing PS-targeted nanotheranostics for potential image-guided drug delivery to treat brain tumors.

Mannose receptor is considered as a hallmark of M2-oriented tumor-associated macrophages (TAMs), but its utility in TAMs was rarely reported. Therefore, deoxymannose (DM), a high-affinity ligand of mannose receptor, was labeled with near-infrared dye cyanine 7 (Cy7), and its feasibility of targeted imaging on TAMs was evaluated in vitro and in vivo. The Cy7-DM was synthesized, and its binding affinity with induced TAMs in vitro, whole-body imaging in xenograft tumor mouse model in vivo, and the cellular localization in dissected tissues were evaluated. We demonstrated a high uptake of Cy7-DM by induced M2 macrophages and TAMs in tumor tissues. In vivo near-infrared live imaging visualized abundant TAMs in tumor lesions instead of inflammatory sites by Cy7-DM imaging, and the quantity of Cy7-DM signals in tumors was significantly higher than that shown in inflammatory sites from 1 to 8 hours of imaging. Our results suggest that mannose could rapidly and specifically target TAMs and is a promising candidate for targeted diagnosis of tumor with rich TAMs.

While cross-sectional imaging with computed tomography (CT) and magnetic resonance imaging is the primary method for diagnosing hepatocellular carcinoma (HCC), they provide little biological insight into this molecularly heterogeneous disease. Nuclear imaging tools that can detect molecular subsets of tumors could greatly improve diagnosis and management of HCC. To this end, we conducted a patient study to determine whether HCC can be resolved using ⁶⁸Ga-citrate positron emission tomography (PET). One patient with recurrent HCC was injected with 300 MBq of ⁶⁸Ga-citrate and imaged with PET/CT 249 minutes post injection. Four (28%) of 14 hepatic lesions were avid for ⁶⁸Ga-citrate. One extrahepatic lesion was not PET avid. The average maximum standardized uptake value (SUV_max) for the lesions was 7.2 (range: 6.2-8.4), while the SUV_max of the normal liver parenchyma was 4.7 and blood pool was 5.7. The avid lesions were not significantly larger than the quiescent lesions, and a prior contrast CT showed uniform enhancement among the lesions, suggesting that tumor signals are due to specific binding of the radiotracer to the transferrin receptor, rather than enhanced vascularity in the tumor microenvironment. Further studies are required in a larger patient cohort to verify the molecular basis of radiotracer uptake and the clinical utility of this tool.

Background: Near-infrared fluorescence (NIRF) imaging combined with enzyme-activatable NIRF probes has yielded promising results in cancer detection.

Objective: To test whether 3-dimensional (3-D) noninvasive in vivo NIRF imaging can detect effects of epidermal growth factor receptor (EGFR) inhibitor on both polypoid and flat tumor load in azoxymethane (AOM)-induced colon tumors or tumors in Apc^Min/+ mice.

Methods: The AOM-injected KK-HIJ mice received EGFR inhibitor diet or chow diet. These and Apc^Min/+ mice were given cathepsin-activatable probes (ProSense 680) before imaging. In vivo imaging was performed using quantitative tomographic NIRF imaging. Ex vivo imaging and histologic examination were performed. Dual imaging by micro computed tomography (CT) and 3D NIRF imaging was used to verify tumor location.

Results: Tumor load reduction by EGFR inhibition was detected ex vivo using cathepsin B probes. In vivo imaging revealed intense activation of probes only in large tumors. Dual imaging with microCT and 3D NIRF imaging improved tumor detection in vivo.

Conclusions: The 3-D NIRF imaging with ProSense 680 can detect and quantify drug effects on colon tumors ex vivo. The NIRF imaging with ProSense 680 probe has limitations as a valid nonendoscopic method for intestinal tumor detection. Combing with other imaging modalities will improve the specificity and sensitivity of intestinal tumor detection in vivo.