Molecular Imaging最新文献

With the rise of fluorescence-guided surgery, it has become evident that different types of fluorescence signals can provide value in the surgical setting. Hereby a different range of targets have been pursued in a great variety of surgical indications. One of the future challenges lies in combining complementary fluorescent readouts during one and the same surgical procedure, so-called multi-wavelength fluorescence guidance. In this review we summarize the current clinical state-of-the-art in multi-wavelength fluorescence guidance, basic technical concepts, possible future extensions of existing clinical indications and impact that the technology can bring to clinical care.

MET, the gene encoding the tyrosine kinase receptor for hepatocyte growth factor, is a susceptibility gene for autism spectrum disorder (ASD). Genetically altered mice with a kinase-inactive Met offer a potential model for understanding neural circuit organization changes in autism. Here, we focus on the somatosensory thalamocortical circuitry because distinct somatosensory sensitivity phenotypes accompany ASD, and this system plays a major role in sensorimotor and social behaviors in mice. We employed resting-state functional magnetic resonance imaging and in vivo high-resolution proton MR spectroscopy to examine neuronal connectivity and neurotransmission of wild-type, heterozygous Met-Emx1, and fully inactive homozygous Met-Emx1 mice. Met-Emx1 brains showed impaired maturation of large-scale somatosensory network connectivity when compared with wild-type controls. Significant sex × genotype interaction in both network features and glutamate/gamma-aminobutyric acid (GABA) balance was observed. Female Met-Emx1 brains showed significant connectivity and glutamate/GABA balance changes in the somatosensory thalamocortical system when compared with wild-type brains. The glutamate/GABA ratio in the thalamus was correlated with the connectivity between the somatosensory cortex and the thalamus in heterozygous Met-Emx1 female brains. The findings support the hypothesis that aberrant functioning of the somatosensory thalamocortical system is at the core of the conspicuous somatosensory behavioral phenotypes observed in Met-Emx1 mice.

Objective: The goal is to evaluate avelumab, an anti-PD-L1 monoclonal immunoglobulin G antibody labeled with zirconium-89 in human PD-L1-expressing cancer cells and mouse xenografts for clinical translation.

Methods: [⁸⁹Zr]Zr-DFO-PD-L1 monoclonal antibody (mAb) was synthesized using avelumab conjugated to desferrioxamine. In vitro binding studies and biodistribution studies were performed with PD-L1+MDA-MB231 cells and MDA-MB231 xenograft mouse models, respectively. Biodistributions were determined at 1, 2, 3, 5, and 7 days post coinjection of [⁸⁹Zr]Zr-DFO-PD-L1 mAb without or with unlabeled avelumab (10, 20, 40, and 400 µg).

Results: [⁸⁹Zr]Zr-DFO-PD-L1 mAb exhibited high affinity (K_d ∼ 0.3 nM) and detected moderate PD-L1 expression levels in MDA-MB231 cells. The spleen and lymph nodes exhibited the highest [⁸⁹Zr]Zr-DFO-PD-L1 mAb uptakes in all time points, while MDA-MB231 tumor uptakes were lower but highly retained. In the unlabeled avelumab dose escalation studies, spleen tissue-muscle ratios decreased in a dose-dependent manner indicating specific [⁸⁹Zr]Zr-DFO-PD-L1 mAb binding to PD-L1. In contrast, lymph node and tumor tissue-muscle ratios increased 4- to 5-fold at 20 and 40 µg avelumab doses.

Conclusions: [⁸⁹Zr]Zr-DFO-PD-L1 mAb exhibited specific and high affinity for PD-L1 in vitro and had target tissue uptakes correlating with PD-L1 expression levels in vivo. [⁸⁹Zr]Zr-DFO-PD-L1 mAb uptake in PD-L1+tumors increased with escalating doses of avelumab.

Expression of programmed cell death ligand 1 (PD-L1) within tumors is an important biomarker for guiding immune checkpoint therapies; however, immunohistochemistry-based methods of detection fail to provide a comprehensive picture of PD-L1 levels in an entire patient. To facilitate quantification of PD-L1 in the whole body, we developed a peptide-based, high-affinity PD-L1 imaging agent labeled with [¹⁸F]fluoride for positron emission tomography (PET) imaging. The parent peptide, WL12, and the nonradioactive analog of the radiotracer, ¹⁹FPy-WL12, inhibit PD-1/PD-L1 interaction at low nanomolar concentrations (half maximal inhibitory concentration [IC₅₀], 26-32 nM). The radiotracer, [¹⁸F]FPy-WL12, was prepared by conjugating 2,3,5,6-tetrafluorophenyl 6-[¹⁸F]fluoronicotinate ([¹⁸F]FPy-TFP) to WL12 and assessed for specificity in vitro in 6 cancer cell lines with varying PD-L1 expression. The uptake of the radiotracer reflected the PD-L1 expression assessed by flow cytometry. Next, we performed the in vivo evaluation of [¹⁸F]FPy-WL12 in mice bearing cancer xenografts by PET imaging, ex vivo biodistribution, and blocking studies. In vivo data demonstrated a PD-L1-specific uptake of [¹⁸F]FPy-WL12 in tumors that is reduced in mice receiving a blocking dose. The majority of [¹⁸F]FPy-WL12 radioactivity was localized in the tumors, liver, and kidneys indicating the need for optimization of the labeling strategy to improve the in vivo pharmacokinetics of the radiotracer.

Epidermal growth factor receptor (EGFR)-targeted cancer therapy requires an accurate estimation of EGFR expression in tumors to identify responsive patients, monitor therapeutic effect, and estimate prognosis. The EGFR molecular imaging is an optimal method for evaluating EGFR expression in vivo accurately and noninvasively. In this review, we discuss the recent advances in EGFR-targeted molecular imaging in cancer, with a special focus on the development of imaging agents, including epidermal growth factor (EGF) ligand, monoclonal antibodies, antibody fragments, Affibody, and small molecules. Each substrate or probe, whether it is an endogenous ligand, antibody, peptide, or small molecule labeled with fluorochrome or radionuclide, has unique advantages and limitations. Antibody-based probes have high affinity but a long metabolic cycle and therefore offer poor imaging quality. Affibody molecules promise to surpass antibody-based probes due to their small size, stable chemical properties, and high affinity to the target. Small-molecule probes are safe, have favorable pharmacokinetics, and show high affinity and specificity, in addition to having an ideal size, but are inadequate for delayed imaging after injection due to their fast clearance.

Noise-induced hearing loss leads to anatomic and physiologic changes in primary auditory cortex (A1) and the adjacent dorsal rostral belt (RB). Since acetylcholine is known to modulate plasticity in other cortical areas, changes in A1 and RB following noise damage may be due to changes in cholinergic receptor expression. We used [³H]scopolamine and [¹⁸F]flubatine binding to measure muscarinic acetylcholine receptor (mAChR) and nicotinic acetylcholine receptor (nAChR) expression, respectively, in guinea pig A1 and RB 3 weeks following unilateral, left ear noise exposure, and a temporary threshold shift in hearing. [³H]Scopolamine binding decreased in right A1 and RB (contralateral to noise) compared to sham controls across all cortical layers. [¹⁸F]Flubatine binding showed a nonsignificant upward trend in right A1 following noise but only significantly increased in right RB and 2 layers of left RB (ipsilateral to noise). This selective response may ultimately influence cortical plasticity and function. The mechanism(s) by which cholinergic receptors are altered following noise exposure remain unknown. However, these data demonstrate noise exposure may differentially influence mAChRs that typically populate interneurons in A1 and RB more than nAChRs that are traditionally located on thalamocortical projections and provide motivation for cholinergic imaging in clinical patient populations of temporary or permanent hearing loss.

Objective: This study evaluated the metabolic parameters and texture features of fluorodeoxyglucose positron emission tomography-computed tomography (PET/CT) for the diagnosis and differentiation of endometrial atypical hyperplasia (EAH), EAH with field cancerization (FC), and stage 1A endometrial carcinoma (EC 1a).

Materials and methods: We retrospectively analyzed the metabolic parameters of PET/CT in 170 patients with diagnoses confirmed by pathology, including 57 cases of EAH (57/170, 33.53%), 45 cases of FC (45/170, 26.47%), and 68 cases of EC 1a (68/170, 40.0%). Then, the texture features of each tumor were extracted and compared with the metabolic parameters and pathological results using nonparametric tests and linear regression analysis. The diagnostic performance was assessed by the area under the curve (AUC) values obtained from receiver operating characteristic analysis.

Results: There were moderate positive correlations between the PET standardized uptake values (SUVpeak, SUVmax, and SUVmean) and postoperative pathological features with correlation coefficients (r_s) of 0.663, 0.651, and 0.651, respectively (P < .001). Total lesion glycolysis showed relatively low correlation with pathological characteristics (r_s = 0.476), whereas metabolic tumor volume and age showed the weakest correlations (r_s = 0.186 and 0.232, respectively). To differentiate between the diagnosis of EAH and FC, SUVmax displayed the largest AUC of 0.857 (sensitivity, 82.2%; specificity, 84.2%). Five texture features were screened out as Percentile 40, Percentile 45, InverseDifferenceMoment_AllDirection_offset 1, InverseDifferenceMoment_angle 45_offset 4, and ClusterProminence_angle 135_offset 7 (P < .001) by linear model of texture analysis (AUC = 0.851; specificity = 0.692; sensitivity = 0.871). To differentiate between the diagnoses of FC and EC 1a, SUVpeak displayed the largest AUC of 0.715 (sensitivity, 67.6%; specificity, 77.8%), and 2 texture features were identified as Percentile 10 and CP_angle 135_offset 7 (AUC = 0.819; specificity = 0.871; sensitivity = 0.766; P < .001).

Conclusions: SUVmax and SUVpeak had the highest diagnostic values for EAH, FC, and EC 1a compared with the other tested parameters. SUVmax, Percentile 40, Percentile 45, InverseDifferenceMoment_AllDirection_offset 1, InverseDifferenceMoment_angle 45_offset 4, and ClusterProminence_angle 135_offset 7 distinguished EAH from FC. SUVpeak, Percentile 10, and ClusterProminence_angle 135_offset 7 distinguished FC from EC 1a. This study showed that the addition of texture features provides valuable information for differentiating EAH, FC, and EC 1a diagnoses.

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.