Molecular Imaging and Biology最新文献

Purpose: Survival and treatment intensity in patients with head and neck squamous cell carcinoma (HNSCC) is determined by the presence of lymph node (LN) metastasis, and as a result surgical removal of potentially affected LN remains a mainstay practice. Fluorescence guided surgery (FGS) using targeted optical agents is an expanding field that shows great potential for aiding diagnosis of metastatic LN. Given variations in fluorescence background, a reference standard for regions of interest is necessary for cross patient comparison. The present study aims to determine whether tissue with native target expression can be used as a background to determine metastatic LN in patients with HNSCC infused with anti-epidermal growth factor receptor (EGFR) targeted imaging agents.

Procedures: Twenty-two patients infused with panitumumab-IRDye800 or cetuximab-IRDye800 prior to surgery were included. Fluorescence imaging and analysis was performed on resected LNs (N = 843) using the submandibular glands (SMG) and skin as reference standard tissue with known EGFR antigen expression.

Results: Sixteen patients (72.7%) had at least one positive LN on final pathology. The LN to SMG (LN/SMG) and LN to skin (LN/skin) ratios were significantly higher in metastatic LN compared to benign LN (p < 0.0001 for both). Using patient-specific ratios to determine an optimal LN/skin cutoff was the most sensitive (95.2%) and directly comparing the LN/skin ratio of all patients to determine a cutoff was the most specific (86.3%).

Conclusions: In HNSCC patients infused with a molecularly targeted fluorescent tracer, endogenous expression of the target antigen can be used as a reference standard to detect LN metastasis. Additionally, the performance of the background in determining metastatic LN can be improved by utilizing patient-specific reference standards.

Purpose: Measuring hepatic flux rates of transportable substrates has the potential for assessing liver function. PET imaging of a PET-enabled substrate may provide a more straightforward measurement of time-dependent substrate concentration through the liver than MRI using an MRI contrast agent. Here we synthesized and evaluated the hepatobiliary transport of a new hepatospecific PET agent designed for stable Cu²⁺ chelation and transport by hepatic OATPs, [⁶⁴Cu]Cu-EOB-NOTA.

Procedures: EOB-NOTA was synthesized, its two enantiomers separated by chiral HPLC, and individually radiolabeled with [⁶⁴Cu]Cu²⁺. Cocktails of each enantiomer of [⁶⁴Cu]Cu-EOB-NOTA and Gd-EOB-DTPA were formulated for simultaneous PET/MRI imaging of hepatic flux by PET and MRI. Two mouse models were evaluated: wild-type mice and mice expressing only human hepatic OATPs.

Results: In wild-type mice, [⁶⁴Cu]Cu-EOB-NOTA hepatic influx and efflux was high, but slower compared to Gd-EOB-DTPA. Neither enantiomer of [⁶⁴Cu]Cu-EOB-NOTA exhibited detectable transport into the liver in mice expressing human OATPs. This was validated by waste clearance studies and in vitro uptake assays in cells engineered to express rodent and human OATPs.

Conclusion: [⁶⁴Cu]Cu-EOB-NOTA exhibited no detectable hepatic uptake by transgenic mice expressing human hepatic transporters. This finding was surprising given the efficient transport of the structurally similar metal chelate Gd-EOB-DTPA, and underscores challenges in the design of imaging molecular probes, including poor predictability for hepatic transport, and the value of validating new agents in mice expressing human hepatic transporters.

Purpose: This study investigated the effects of laterality, age, gender, BMI, and physical activity level on iliac bone turnover using [¹⁸F]NaF PET/CT.

Procedures: Fifty-nine males and 44 females from the CAMONA study were analyzed. A region of interest (ROI) was drawn to segment the iliac bone using Hounsfield unit thresholds and morphological closing algorithm. [¹⁸F]NaF SUVmean was compared between the left and right iliac bones using a paired t-test, while Pearson correlation coefficient assessed changes with age, BMI, and physical activity level.

Results: [¹⁸F]NaF uptake was higher in right iliac bone than left in males, females, and the combined-group. In males, SUVmean was 2.98 ± 1.63 (1.1-7.87) on left and 3.71 ± 1.49 (1.49-3.7) on right. In females, SUVmean was 2.59 ± 1.14 (0.88-6.27) on left and 3.72 ± 1.04 (2.22-6.51) on right. Combined, SUVmean was 2.81 ± 1.44 (0.88-7.87) on left and 3.71 ± 1.31 (0.89-8.07) on right. [¹⁸F]NaF uptake negatively correlated with age (right: r = - 0.27, P = 0.006; left: r = - 0.22, P = 0.02), stronger in females (right: r = - 0.30, P = 0.04; left: r = - 0.31, P = 0.04) than males (right: r = - 0.26, P = 0.04; left: r = - 0.18, P = 0.18). SUVmean correlated positively with BMI in males (right: r = 0.47, P = 0.0002; left: r = 0.38, P = 0.0027), females (right: r = 0.36, P = 0.0168; left: r = 0.30, P = 0.0505), and combined-group (right: r = 0.43, P < 0.0001; left: r = 0.37, P = 0.0001). No significant correlation was found between SUVmean and physical activity in males, while in females, a negative correlation was observed on left (r = - 0.37, P = 0.0390) but not on right (r = - 0.27, P = 0.1302), and when combined, the correlation remained significant on left (r = - 0.24, P = 0.0372) but not on right (r = - 0.16, P = 0.1541).

Conclusions: [¹⁸F]NaF uptake was higher in the right iliac bone and declined with age, particularly in females. The positive correlation between SUVmean and BMI; and the negative correlation between SUVmean and physical activity suggest metabolic influences on bone turnover. [¹⁸F]NaF PET/CT may serve as a tool for assessing bone metabolism and turnover in asymptomatic individuals.

Purpose: Heat stroke is the most serious heat-related illness and is recognized as a worldwide public concern as global temperatures continue to rise. Although the clinical neurological complications of heat stroke are relatively well described, a limited number of studies exist that document imaging findings. Therefore, in this preclinical study, we aimed to identify the imaging findings of ¹⁸F-FDG brain PET following heat stroke and elucidate the utility of FDG PET in the evaluation of heat stroke-induced brain injury.

Methods: Heat stroke was induced in Sprague Dawley rats by placing them in a hot and humid chamber maintained without food and water until they exhibited the heat stroke onset diagnostic criterion. Three hours after the induction ended, ¹⁸F-FDG brain PET images were acquired in 7 controls and 14 rats with heat stroke. Between groups, region-based (standardized uptake values were normalized to the whole brain and SUV of the whole brain (SUV_WB), and voxel-based analyses were performed.

Results: Of the 14 rats with heat stroke, 8 survived, whereas 6 did not. In the region-based and voxel-base analyses, the rats that did not survive showed significantly higher SUVR_HB in the hypothalamus and significantly lower SUVR_HB in several cortical regions than the controls as well as the survived rats. In the region-based analysis, the survived rats showed a significant increase or decrease in SUVR_HB compared to the controls in a few cortical regions. However, no difference was observed in the voxel-based analysis.

Conclusions: The 3-h post-injury PET scan showed a distinctly different regional distribution of ¹⁸F-FDG in the brains of lethally injured heat stroke rats compared to the controls as well as the survived rats. The ¹⁸F-FDG brain PET may have the potential to provide early indicators of catastrophic injury and reflect the early neurological pathophysiology of heat stroke.

Purpose: Since the avid uptake of ⁶⁸Ga-labeled fibroblast activation protein inhibitor (⁶⁸Ga-FAPI-04) observed in female reproductive organs, our objectives were to investigate the physiological uptake characteristics and provide preliminary reference ranges for clinical use.

Procedures: We reviewed the findings of female patients who underwent ⁶⁸Ga-FAPI-04 PET/CT at our institution between April 2022 and June 2023. The standard uptake value (SUV) of reproductive organs and menstrual information were collected. All patients were categorized into reproductive period group, perimenopause group, and postmenopause group. We analysed the uptake levels among the three groups, and their association with age and menstrual cycle.

Results: A total of 109 patients were included in this study. Higher ovarian SUVs were detected in reproductive patients (SUV_right: 2.75 ± 0.84, IQR: 1.39-5.26; SUV_left: 2.72, IQR: 2.34-3.20; p = 0.315) than in postmenopausal patients (SUV_right: 2.27, IQR: 2.01-2.75; SUV_left: 2.38 ± 0.55, IQR: 1.35-3.60; p = 0.767), as well as uterine ⁶⁸Ga-FAPI-04 accumulations. The SUVs of uterine fundus and corpus were approximately three times higher than that of the cervix. In reproductive period group, higher SUVs were observed in bilateral ovaries around the ovulatory phase to the early luteal phase, and higher uterine SUVs were noted in the menstrual and proliferative phases. The SUVs in all reproductive organs (except the ovaries) showed significant negative correlations with age in all patients (all p < 0.01).

Conclusions: ⁶⁸Ga-FAPI-04 SUVs in reproductive organs are higher in premenopausal patients than in postmenopausal patients. The ⁶⁸Ga-FAPI-04 accumulation in reproductive organs might be associated with menstrual cycle. Including more patients from different menstrual phases could contribute to investigating the uptake characteristics and their underlying mechanisms.

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.