Molecular Imaging and Biology最新文献

Purpose: Schizophrenia (SCZ) is a severe psychiatric disorder marked by abnormal dopamine synthesis, measurable through [¹⁸F]FDOPA PET imaging. This imaging technique has been proposed as a biomarker for treatment stratification in SCZ, where one-third of patients respond poorly to standard antipsychotics. This study explores the use of radiomics on [¹⁸F]FDOPA PET data to examine dopamine synthesis in SCZ and predict antipsychotic response.

Methods: We analysed 273 [¹⁸F]FDOPA PET scans from healthy controls (n = 138) and SCZ patients (n = 135) from multiple cohorts, including first-episode psychosis cases. Radiomic features from striatal regions were extracted using the MIRP Python package. Reproducibility was assessed with test-retest scans, selecting features with an intraclass correlation coefficient (ICC) > 0.80. These features were grouped via hierarchical clustering based on Spearman correlation. Regression analysis evaluated sex and age effects on radiomic features. Predictive power for treatment response was tested and compared to standard imaging analysis obtained from the Standardised Uptake Value ratio (SUVr) of striatal over cerebellar tracer activity.

Results: Out of 177 features, 15 met the ICC criteria (ICC: 0.81-0.99). Age and sex influenced features in patients but not in controls. The best performance were was by the GLCM joint maximum feature, which effectively differentiated responders from non-responders (AUC: 0.66-0.87), but did not reach statistical significance in classification over SUVr.

Conclusion: Radiomic analysis of [¹⁸F]FDOPA PET supports its use as a biomarker for assessing antipsychotic efficacy in schizophrenia, highlighting differential striatal tracer uptake based on patient response. While it provides modest classification improvements over standard imaging, further validation in larger datasets and integration with multivariate classification algorithms are needed.

Purpose: In this study, we examined changes in glial energy metabolism in neonatal mouse brain images obtained under pathological conditions following intranasal administration of the radiotracer [2-¹⁴C]acetate.

Procedures: [2-¹⁴C]acetate was administered via the mouse nasal cavity, after which autoradiograms of the brain of 7-day-old mice were obtained. Radio thin-layer chromatography was applied for metabolite analysis of brain radioactivity. We also compared brain uptake of [2-¹⁴C]acetate when administrated intranasally and intravenously in 3-week-old mice. To confirm selective uptake by glial cells, [2-¹⁴C]acetate was injected into the nasal cavity of mice injected with a glial toxin in the brain. Pentylenetetrazole (PTZ) was applied to induce seizures.

Results: Intranasally administered [2-¹⁴C]acetate was rapidly incorporated into the brains of 7-day-old mice, reaching its highest uptake level 20 min after administration. After 20 min of intranasal [2-¹⁴C]acetate administration, glutamate and glutamine accounted for 32 ± 2.5% and 30 ± 3.4% of total brain radioactivity, respectively. There was no difference in the radioactivity distribution in the brain between intranasal and intravenous administration, except in the ventral olfactory bulb in 3-week-old mice. Microinjection of the glial-specific toxin fluorocitrate reduced the accumulation of radioactivity in the brain by 60% following intranasal administration in 3-week-old mice. The uptake of [2-¹⁴C]acetate in the brains of 7-day-old mice significantly decreased 30 min after systemic PTZ administration, suggesting a decrease in energy metabolism in glial cells during seizures.

Conclusions: Quantitative images of biological functions in the neonatal mouse brain can be obtained by intranasal administration. This technique allowed the observation of a decrease in acetate uptake associated with convulsive seizures. The results of this study could be applied to the imaging of biological brain functions and research on neurological disorders using labeled probes in neonatal mice.

Purpose: Plectin is traditionally an intracellular cytoskeletal protein that maintains cell structure and stability. However, we and others have identified its surface-localized form in cancer (CSP), where it influences cell adhesion, migration, immune response, and tumor signaling. CSP-positive tumors (pancreatic, lung, ovarian, and breast cancers) contribute to over 3 million annual deaths, highlighting its clinical relevance. This phase 0 study aimed to evaluate PTP-01's ability to target CSP in pancreatic tumors, despite their dense desmoplastic stroma, and to estimate CSP density and tumor vascularity.

Methods: Pancreatic cancer patients (n = 3) received an intravenous injection of 100 µg PTP-01 labeled with 370 MBq ¹¹¹In one day before resection. Whole-body planar scintigraphy and SPECT imaging were performed at multiple time points. Resected tumors and adjacent tissues were collected 28 h post-injection. Blood and urine samples were obtained for pharmacokinetic analysis. Tissue biodistribution was assessed using whole-body SPECT scans.

Results: PTP-01 injection caused no reported adverse events. Uptake was primarily observed in the kidneys, liver, and bladder, with some tumor uptake. CSP density in tumors was estimated at 10⁶ molecules per cell. The elimination half-life (T₁/₂) ranged from 5 to 22 h across patients.

Conclusion: PTP-01 imaging of pancreatic tumors revealed the ability of a targeted agent to bind to CSP. Further, CSP density in tumors was estimated to be on par with other surface molecules such as Her2 with effective targeted therapies. This study suggests that CSP is a highly expressed, accessible molecule for the development of targeted therapies such as antibodies or antibody-drug conjugates.

Purpose: Imaging reporters have been widely employed in cancer research to monitor real-time tumor burden and metastatic spread. These tools offer a valuable approach for non-invasive imaging of tumor dynamics over time. With the established understanding that tumor immunology plays a critical role in cancer progression, it is essential to ensure that the chosen imaging reporters used to study tumor-immune interactions do not inadvertently elicit an immune response. This study aimed to investigate the immune response to bioluminescence reporters used for in vivo tracking of tumor cells in immunocompetent murine models.

Procedures: The in vitro and in vivo growth effects of two stably expressed bioluminescence reporter genes, a red-shifted firefly luciferase and a click beetle green luciferase, were evaluated in four different cancer cell lines. Differences in parental and reporter-expressing cancer cell immune cell composition, activation, and secreted cytokine levels were evaluated using flow cytometry, cytokine arrays and ELISAs.

Results: The data revealed no significant differences in in vitro cell proliferation between parental and reporter cancer cell lines. In vivo subcutaneous tumor growth was not observed in tumor cells stably expressing the red-shifted firefly luciferase. Cells labeled with click beetle green luciferase demonstrated no significant differences in in vivo subcutaneous tumor growth compared to parental cells. Tumor cells expressing red-shifted firefly luciferase induced an increase in activated and cytotoxic T cells compared to parental and click beetle green luciferase, suggesting enhanced immunogenicity. Furthermore, the tumor-immune composition and cytokine production were similar between parental and click beetle green luciferase-labeled tumor cells.

Conclusions: These findings demonstrate that the stable expression of click beetle green luciferase in cancer cells, in contrast to red-shifted firefly luciferase, has minimal immunogenicity and does not alter tumor development in immunocompetent mice. We report detailed characterization studies of bioluminescence reporter cells, providing essential considerations for their use in investigating tumor-immune interactions in syngeneic murine tumor models.

Purpose: Two types of asymmetry index (AI) have been utilized in evaluating cerebral function in ischemic cerebrovascular disease, however, few data exist on the differences between these AI measures. This study aimed to compare the two AIs in assessing PET cerebral metabolism and their correlation with clinical scales, to explore their potential value and applications in clinical settings.

Procedures: Seventy patients diagnosed with subacute and chronic ischemic stroke were retrospectively analyzed. All patients underwent 2-deoxy- 2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) PET/MR scans and were assessed using the National Institutes of Health Stroke Scale (NIHSS) and the Modified Rankin Scale (mRS). Nineteen patients underwent a repeat [¹⁸F]FDG PET/MR scan one year later. Two voxel-wise AI methods, designated as AI₁ and AI₂, were calculated based on standardized uptake value ratio (SUVR). The hypometabolism on affected side assessed by different AI methods were compared. The correlations between the hypometabolism and the clinical scores were analyzed.

Results: The volume and percentage of decreased [¹⁸F]FDG metabolism assessed by AI₂ was larger than that obtained from AI₁ (all p < 0.0001). The correlation coefficients between the clinical scores and the decreased metabolism in temporal and parietal lobes assessed by AI₁ method were all higher than those from AI₂. In addition, the improved follow-up patients showed more pronounced metabolic improvement as assessed by AI₁.

Conclusions: The assessment of cerebral [¹⁸F]FDG metabolism in patients with unilateral internal carotid/middle cerebral artery steno-occlusion to reflect clinical neurological function using the AI₁ method demonstrated superior performance in comparison to the AI₂ method.

Purpose: Positron Emission Tomography (PET), a crucial tool in molecular brain imaging, has evolved into a hybrid system through integration with functional MRI (fMRI). This advancement facilitates the simultaneous recording of molecular and functional data in animal models, offering insights into neuroreceptor and neurotransmitter dynamics and their effects on brain function. While mechanical ventilation is often used in small animal fMRI to stabilize physiological blood gas levels, its effects on PET tracer kinetics remain underexplored.

Procedures: This study examines the kinetics of [¹¹C]raclopride, a dopamine-sensitive PET tracer targeting D2/D3 receptors, under various respiratory conditions and anesthesia protocols frequently used in small animal fMRI and PET.

Results: Results indicate significant variations in tracer kinetics: increased peak levels, a shorter time to peak, and a faster tracer equilibrium in standard uptake value ratio were observed in spontaneously breathing animals versus those under mechanical ventilation. The anesthesia type also strongly influenced the tracer kinetics: α-chloralose anesthesia reduced brain uptake, whereas isoflurane led to a more rapid equilibrium.

Conclusions: These findings underscore the profound impact of mechanical ventilation and anesthesia selection on PET tracer kinetics in hybrid PET/fMRI studies. The study highlights that those protocols established for fMRI are not directly transferable to PET imaging in small animals, emphasizing the necessity for a careful investigation of the influence of anesthesia and ventilation techniques on tracer kinetics.

Aim: This study examines the combination of FES-PET and FDG-PET as complementary imaging for detection of metastatic ILC.

Methods: We retrospectively evaluated FES and FDG uptake in patients with metastatic ILC from an estrogen receptor (ER) positive primary tumor. We classified lesions into three categories (FES high/FDG low, FES high/FDG high, FES low/FDG low) using SUVmax cut-off values of 1.5 for FES and 5.0 for FDG. Qualitative evaluation included examination of the difference in the extent of disease between FES and FDG.

Results: Of the 38 patients, 82% had FES uptake in all tumor sites identified by FDG, with 18% lacking FES uptake in at least one lesion. Mean (range) SUVmax for FES and FDG was 4.0 (0.67-10.6) and 4.6 (1.3-12.5), respectively. The majority of ILC patients (25/38), had lesions with FES high/FDG low uptake, consistent with the strongly ER + indolent nature of ILC. Patients with disease classified as FES high/FDG low had longer median overall survival (OS) (3.2 years) and progression-free survival (PFS) (1.5 years) than FES high/FDG high (OS = 2.1 years and PFS = 0.46 years). The median overall OS for all patients was 3.0 years (95% CI 2.5, 4.8) and PFS of 1.3 years (95% CI 0.6, 2.5). 8 patients (21%) had qualitatively more extensive disease by FES-PET.

Conclusions: Our findings suggest that both FES-PET and FDG-PET can identify metastatic ILC and be useful in detecting the pattern and extent of disease. The imaging combination provides additional information for prognosis and clinical decision making, balancing suitability for endocrine therapy and aggressiveness/indolence of disease.

Purpose: Lymph node (LN) biopsy is the gold standard for diagnosing metastasis. While ultrasound imaging is a non-invasive method for real-time LN metastasis diagnosis and tumor assessment, its accuracy depends on operator skill and system settings. Quantitative ultrasound can characterize tissue microstructure changes due to tumors, offering operator-independent parameters, and one of the quantitative ultrasound methods, the backscatter coefficient, is necessary to compensate for tissue attenuation. However, the change in the attenuation coefficient (AC) in the tumor growth is uncertain. Using in vivo high-frequency ultrasound (25 MHz) measurement and scanning acoustic microscopy (80 and 300 MHz) for ex vivo samples, we aim to investigate how tumor growth is linked to the attenuation and acoustic properties such as acoustic impedance and speed of sound related to ultrasonic wave propagation.

Procedures: FM3 A-Luc mammary carcinoma cells were inoculated into the subiliac LNs of mice, and tumor progression was monitored over time. Bioluminescence imaging was used to assess tumor growth, while ultrasound measurements focused on estimating AC and other acoustic properties.

Results: Results indicated that the mean of AC decreased, and its standard deviation increased as tumors grew, correlating with bioluminescence intensity. Furthermore, acoustic impedance and speed of sound varied between normal and tumor tissues, revealing differences in tissue microstructure from the histopathological images.

Conclusions: The finding of a decrease in AC observed with tumor growth may play a crucial role in enhancing the accuracy of quantitative ultrasound on attenuation compensation, potentially improving the differentiation between metastatic and non-metastatic LNs.

Purpose: Carbonic anhydrase IX (CAIX) which is high expression in the most of hypoxic tumor than normal tissue, promoting the growth, invasion, and metastasis of the tumor. Therefore, the study aimed to evaluate the retention and diagnostic ability of [¹²⁴I]I-XYIMSR- 01 in CAIX-overexpression tumor by using positron emission tomography (PET) imaging.

Procedures: [^124/125I]I-XYIMSR- 01 was labeled by ^124/125I, and its CAIX-targeting properties in different cell lines were assayed by cell uptaken study. Its diagnose and retention ability in vivo were verified in different CAIX-expression models using PET imaging and biodistribution study. Pathological tissues were obtained for immunohistochemical (IHC) and Hematoxylin-Eosin (HE) staining to explore the relationship between CAIX and hypoxic, and further analyze PET/CT results.

Results: [¹²⁴I]I-XYIMSR- 01 was obtained with high specific activity, good radiochemical purity, and good stability. The uptake of of [¹²⁴I]I-XYIMSR- 01 in HT- 29 cells, which have high CAIX expression, was significant higher than that in HCT116 cells with low CAIX expression (12.78 ± 0.47 vs 1.06 ± 0.10, p = 0.000, at 1 h). This indicated that the probe has good targeting capability and specificity for CAIX. In Micro-PET imaging, clear molecular images lasting for 48 h were achieved in HT29 model. Quantitative biodistribution results showed that the tumor and digestive tract background tissues had a good signal-to-noise ratio within 24 h after injection, indicating [¹²⁴I]I-XYIMSR- 01 could enable delayed imaging in digestive tract tumors (tumor-to-small intestine: 8.79 ± 0.98). Tumors uptakes were also confirmed by IHC pathology.

Conclusion: The study have shown that [¹²⁴I]I-XYIMSR- 01 is an ideal molecular probe for tumor hypoxia, enabling long-term dynamic monitoring and imaging of hypoxic tumors.

Purpose: Evaluation of ¹⁸F-FAPI PET/CT imaging in sorafenib-induced cardiac dysfunction in hepatocellular carcinoma (HCC) patients, and compared with ¹⁸F-FDG PET/CT.

Procedures: This retrospective study enrolled 75 HCC patients treated with sorafenib at our institution from June 2021 to June 2023. All patients underwent ¹⁸F-FDG PET/CT six months after treatment, followed by ¹⁸F-FAPI PET/CT within the subsequent week. Patients were divided into cardiac dysfunction group and control group based on the definition of cancer therapy-related cardiac dysfunction (CTRCD). Myocardial uptake parameters on ¹⁸F-FDG and ¹⁸F-FAPI PET/CT were compared between the two groups. The primary endpoint was the occurrence of major adverse cardiac events (MACEs), and the secondary endpoint was all-cause mortality, with follow-up at 30, 90, and 180 days after the PET/CT examinations.

Results: This study ultimately enrolled 47 patients, with the cardiac dysfunction group (n = 9) and control group (n = 38) demonstrating significant differences in myocardial ¹⁸F-FAPI high uptake, left ventricular (LV) ¹⁸F-FDG SUV, LV/liver ¹⁸F-FDG SUV, myocardial ¹⁸F-FAPI SUV, myocardial/aorta ¹⁸F-FAPI SUV, and myocardial/liver ¹⁸F-FAPI SUV. One year after treatment, the incidence of MACEs was slightly higher in the group with high ¹⁸F-FAPI myocardial uptake compared to the low uptake group (19.5% vs. 14.0%, log-rank p = 0.621), and the overall survival rate was lower in the high uptake group compared to the low uptake group (57.9% vs. 65.8%, log-rank p = 0.503).

Conclusions: The myocardial uptake parameters of ¹⁸F-FDG and ¹⁸F-FAPI PET/CT are helpful in evaluating sorafenib-induced cardiac dysfunction in HCC patients. The level of ¹⁸F-FAPI myocardial uptake has potential value in predicting post-treatment cardiotoxicity and overall survival prognosis in HCC patients.