Molecular Imaging最新文献

Objective: To evaluate the preclinical value of ¹⁸F-fluoropropionic acid (¹⁸F-FPA) and ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) for imaging HCCs.

Methods: The ¹⁸F-FPA and ¹⁸F-FDG uptake patterns in 3 HCC cell lines (Hep3B, HepG2, and SK-Hep1) were assessed in vitro and in vivo. The ¹⁸F-FPA uptake mechanism was investigated using inhibition experiments with orlistat and 5-tetradecyloxy-2-furoic acid. The ¹⁸F-FPA PET imaging was performed in different tumor animal models and compared with ¹⁸F-FDG. We also evaluated the expressions of glucose transporter-1 (GLUT1), fatty acid synthase (FASN), and matrix metalloproteinase-2 (MMP2) in these cell lines.

Results: In vitro experiments showed that the radiotracer uptake patterns were complementary in the HCC cell lines. Orlistat and 5-tetradecyloxy-2-furoic acid decreased the uptake of ¹⁸F-FPA. The tumor-to-liver ratio of ¹⁸F-FPA was superior to that of ¹⁸F-FDG in the SK-Hep1 and HepG2 tumors ( P < .05). However, in the Hep3B tumors, the tumor-to-liver normalized uptake of ¹⁸F-FDG was higher than ¹⁸F-FPA ( P < .01). FASN was highly expressed in cell lines with high ¹⁸F-FPA uptake, whereas GLUT1 was highly expressed in cell lines with high ¹⁸F-FDG uptake. The ¹⁸F-FPA uptake correlated with FASN ( r = 0.89, P = .014) and MMP2 ( r = 0.77, P = .002) expressions.

Conclusions: PET imaging with ¹⁸F-FPA combined with ¹⁸F-FDG can be an alternative for detecting HCC.

Objectives: Increasing interests have been focused on using artificial intelligence (AI) to extend prognostic value of medical imaging. Feature extraction is a critical step for successful application of AI. The aim of this study was to explore several metabolic parameters measured by ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) as potential AI features in predicting the effectiveness of chemotherapy in patients with non-small cell lung cancer (NSCLC).

Methods: A set of metabolic parameters of PET/CT and clinical characteristics were detected from 137 patients with NSCLC treated with at least 1 cycle of chemotherapy. Survival receiver-operating characteristic (ROC) analysis was used to define the more significant parameters chosen for the following survival analysis. Patient survival was analyzed by Kaplan-Meier method, log-rank test, and Cox regression.

Results: Survival ROC showed that maximum standardized uptake value (SUVmax), metabolic tumor volume 50% (MTV50), and total lesion glycolysis 50% (TLG50) had larger area under the curve, and the optimal cutoff values were 11.72, 4.04, and 34.55, respectively. Univariate and multivariate analyses synergistically showed that late PET/CT stage and MTV50 >4.04 were independent factors of poor survival in patients with NSCLC who received chemotherapy.

Conclusions: Several potential prognostic biomarkers of PET/CT imaging have been extracted for predicting survival and selecting patients with NSCLC who are more likely to benefit from chemotherapy. The identification may accelerate the development of AI methods to improve treatment outcome for NSCLC.

Objective: Oxidative stress plays an important role in the onset of many neuronal and peripheral disorders. We examined the feasibility of obtaining semiquantitative fluorescent images of reactive oxygen species (ROS) generation in mouse brain and kidney utilizing a planar laser scanner and dihydroethidium (DHE).

Methods: To investigate ROS generation in brain, sodium nitroprusside was injected into the striatum. Dihydroethidium was injected into the tail vein. After DHE injection, tissue slices were analyzed utilizing a planar laser scanner. For kidney study, cis-diamminedichloroplatinum [II] (cisplatin) was intraperitoneally administrated into mice.

Results: Clear and semiquantitative fluorescent images of ROS generation in the mouse brain and kidney were obtained. Furthermore, the fluorescence intensity was stable and not affected by fading. Sodium nitroprusside induced approximately 6 times the fluorescence accumulation in the brain. Cisplatin caused renal injury in all mice, and in comparison with control mice, more than 10 times fluorescence accumulation was observed in the renal medulla with tubular necrosis and vacuolization.

Conclusions: We successfully obtained ex vivo semiquantitative fluorescent images of ROS generation utilizing a planar laser scanner and DHE. This simple method is useful for ROS detection in several ROS-related animal models and would be applicable to a variety of biochemical processes.

Positron emission tomography (PET) imaging with biological macromolecules greatly expands the possibilities of molecular imaging. There are, however, practical aspects limiting the potential of the approach, including the dosimetric consequences of the slow kinetics of radiolabeled biomacromolecules. Pretargeting strategies have led to impactful improvements in the field but are themselves limited by shortcomings of available bioconjugation methodology. We report our initial findings concerning the suitability of the adamantane/cucurbit[7]uril system for pretargeted immuno-PET imaging and provide proof-of-concept PET/computed tomography imaging experiments to establish the stability and rapid formation of host-guest complexes in vivo. The adamantane/cucurbit[7]uril system itself without antibody conjugation has shown remarkably fast association kinetics and clearance in vivo. We further demonstrate the modulation of biodistribution achievable by cucurbituril complexation with relevance for pharmaceutical formulation as well as the radiosynthetic access to relevant reporter molecules labeled with ¹¹C or ¹⁸F. This work, an early proof-of-concept, supports the notion that the adamantane/cucurbit[7]uril system warrants further exploration in pretargeted PET imaging applications.

Oral cancer is one of the most common cancers globally. Survival rates for patients are directly correlated with stage of diagnosis; despite this knowledge, 60% of individuals are presenting with late-stage disease. Currently, the initial evaluation of a questionable lesion is performed by a conventional visual examination with white light. If a lesion is deemed suspicious, a biopsy is taken for diagnosis. However, not all lesions present suspicious under visual white light examination, and there is limited specificity in differentiating between benign and malignant transformations. Several vital dyes, light-based detection systems, and cytology evaluation methods have been formulated to aid in the visualization process, but their lack of specific biomarkers resulted in high false-positive rates and thus limits their reliability as screening and guidance tools. In this review, we will analyze the current methodologies and demonstrate the need for specific intraoral imaging agents to aid in screening and diagnosis to identify patients earlier. Several novel molecular imaging agents will be presented as, by result of their molecular targeting, they aim to have high specificity for tumor pathways and can support in identifying dysplastic/cancerous lesions and guiding visualization of biopsy sites. Imaging agents that are easy to use, inexpensive, noninvasive, and specific can be utilized to increase the number of patients who are screened and monitored in a variety of different environments, with the ultimate goal of increasing early detection.

Metastasis is the most common cause of death for patients with cancer. To fully understand the steps involved in metastatic dissemination, in vivo models are required, of which murine ones are the most common. Therefore, preclinical imaging methods such as magnetic resonance imaging (MRI) have mainly been developed for small mammals and their potential to monitor cancer growth and metastasis in nonmammalian models is not fully harnessed. We have here used MRI to measure primary neuroblastoma tumor size and metastasis in a chick embryo model. We compared its sensitivity and accuracy to end-point fluorescence detection upon dissection. Human neuroblastoma cells labeled with green fluorescent protein (GFP) and micron-sized iron particles were implanted on the extraembryonic chorioallantoic membrane of the chick at E7. T₂ RARE, T₂-weighted fast low angle shot (FLASH) as well as time-of-flight MR angiography imaging were applied at E14. Micron-sized iron particle labeling of neuroblastoma cells allowed in ovo observation of the primary tumor and tumor volume measurement noninvasively. Moreover, T₂ weighted and FLASH imaging permitted the detection of small metastatic deposits in the chick embryo, thereby reinforcing the potential of this convenient, 3R compliant, in vivo model for cancer research.

Objective: To investigate the value of 2-(3-[¹⁸F]fluoropropyl)-2-methyl-malonic acid ([¹⁸F]ML-8) positron emission tomography (PET) imaging of rat pulmonary fibrosis.

Methods: Male Sprague-Dawley rats were divided into 2 groups, including pulmonary fibrosis model group and control group. The rat model was established by an intratracheal instillation of bleomycin (BLM). Control rats were treated with saline. Positron emission tomography/computed tomography (CT) with [¹⁸F]ML-8 or ¹⁸F-fluorodeoxyglucose ([¹⁸F]FDG) was performed on 2 groups. After PET/CT imaging, lung tissues were collected for histologic examination. Data were analyzed and comparisons between 2 groups were performed using Student t test.

Results: Bleomycin-treated rats showed a higher lung uptake of [¹⁸F]ML-8 than control rats ( P < .05). In BLM-treated rats, the lung to muscle relative uptake ratio of [¹⁸F]ML-8 was also higher than that of [¹⁸F]FDG ( P < .05). Pathological examination showed overproliferation of fibroblasts and deposition of collagen in lungs from BLM-treated rats. Compared to control rats, BLM-treated rats had higher lung hydroxyproline content ( P < .05). Immunofluorescence staining indicated more apoptotic cells in BLM-treated rats than those in control rats. Moreover, the apoptosis rate of lung tissues obtained from BLM-treated rats was higher than that from control rats ( P < .05).

Conclusions: 2-(3-[¹⁸F]fluoropropyl)-2-methyl-malonic acid PET/CT could be used for noninvasive diagnosis of pulmonary fibrosis in a rat model.

One-third of patients with heart disease develop heart failure, which is diagnosed through imaging and detection of circulating biomarkers. Imaging strategies reveal morphologic and functional changes but fall short of detecting molecular abnormalities that can lead to heart failure, and circulating biomarkers are not cardiac specific. Thus, there is critical need for biomarkers that are endogenous to myocardial tissues. The cardiac growth hormone secretagogue receptor 1a (GHSR1a), which binds the hormone ghrelin, is a potential biomarker for heart failure. We have synthesized and characterized a novel ghrelin peptidomimetic tracer, an ¹⁸F-labeled analogue of G-7039, for positron emission tomography (PET) imaging of cardiac GHSR1a. In vitro analysis showed enhanced serum stability compared to natural ghrelin and significantly increased cellular uptake in GHSR1a-expressing OVCAR cells. Biodistribution studies in mice showed that tissue uptake of the tracer was independent of circulating ghrelin levels, and there was negligible cardiac uptake and high uptake in the liver, intestines, and kidneys. Specificity of tracer uptake was assessed using ghsr ^-/- mice; both static and dynamic PET imaging revealed no difference in cardiac uptake, and there was no significant correlation between cardiac standardized uptake values and GHSR1a expression. Our study lays the groundwork for further refinement of peptidomimetic PET tracers targeting cardiac GHSR1a.

Targeted therapies hold great promise for cancer treatment and may exhibit even greater efficacy when combined with patient selection tools. The clinical impact of identifying likely responders includes reducing the number of unnecessary and ineffective therapies as well as more accurately determining drug effects. Positron emission tomography (PET) imaging using zirconium-89 radiolabeled monoclonal antibodies (mAbs), also referred to as zirconium-89 (⁸⁹Zr)-immuno-PET, provides a potential biomarker to measure target expression and verify optimal delivery of targeted agents to tumors. Antibody-drug conjugates (ADCs) combine the high affinity and specificity of mAbs with the potency of cytotoxic drugs to target tumor-expressing antigen and destroy cancer cells. Thus, ⁸⁹Zr-immuno-PET of whole-body biodistribution, pharmacokinetics, and tumor targeting of antibodies and ADCs to predict toxicity and efficacy could help guide individualized treatment. Here, we review how ⁸⁹Zr-immuno-PET is being used as a companion diagnostic with the development of ADCs. Furthermore, we discuss how ⁸⁹Zr-immuno-PET may be utilized in future clinical trials as an adjunct tool with novel ADCs to select cancer patients who have the greatest potential to benefit from treatment and improve ADC dosing regimens.

Placental oxygenation varies throughout pregnancy. The detection of early changes in placental oxygenation as pregnancy progresses is important for early identification of preeclampsia or other complications. This invited commentary discusses a recent preclinical study on the application of 3-dimensional photoacoustic imaging (PAI) for assessment of regional variations in placental oxygenation and longitudinal analysis of differences in placental oxygenation throughout normal pregnancy and pregnancy associated with hypertension or placental insufficiency in mice. Three-dimensional PAI more accurately reflects oxygen saturation, hemoglobin concentrations, and changes in oxygen saturation in whole placenta compared to 2-dimensional imaging. These studies suggest that PAI is a sensitive tool to detect different levels of oxygen saturation in the placental and fetal vasculature in pathologic and normal pregnancy in mice.