Molecular Imaging And Biology[JOURNAL]
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200 papers
Visions by WIMIN: Imposter Phenomenon.
Akam-Baxter E, O'Brien CM, Sinharay S … +9 more , Clavijo-Jordan V, Rodriguez SB, Ijoma JN, Kustagi A, Sahn M, Diop F, Mack K, Malonza N, Alvarez NH
Mol Imaging Biol · 2025 Feb · PMID 39777596 · Publisher ↗
The imposter phenomenon (IP) is a destructive set of beliefs, traits, and experiences in which high-achieving individuals fail to internalize their accomplishments and falsely perceive themselves as frauds. IP is a funct...
The imposter phenomenon (IP) is a destructive set of beliefs, traits, and experiences in which high-achieving individuals fail to internalize their accomplishments and falsely perceive themselves as frauds. IP is a function of underrepresentation and contributes to and perpetuates a cycle of low self-worth, perfectionism, and anxiety, all of which negatively affect job performance and reinforce the IP cycle. Mitigating the deleterious effects of IP requires first naming this phenomenon and recognizing the patterns of IP. In this article, we summarize pertinent social science literature on this topic and share experiences of IP as told by the authors and anonymous contributors. We highlight the potential destructive effects of IP, as well as strategies that mentors and trainees can utilize to counter this phenomenon.
Evaluation of Brain Impairment Using Proton Exchange Rate MRI in a Kainic Acid-Induced Rat Model of Epilepsy.
Yang H, Wu Q, Li L … +1 more , Wu Y
Mol Imaging Biol · 2025 Feb · PMID 39747781 · Publisher ↗
PURPOSE: Proton exchange rate (K) is a valuable biophysical metric. K MRI may augment conventional structural MRI by revealing brain impairments at the molecular level. This study aimed to investigate the feasibility of...
PURPOSE: Proton exchange rate (K) is a valuable biophysical metric. K MRI may augment conventional structural MRI by revealing brain impairments at the molecular level. This study aimed to investigate the feasibility of K MRI in evaluating brain injuries at multiple epilepsy stages. PROCEDURES: Six adult rats with epilepsy induced by intra-amygdalae administration of kainic acid (KA) underwent MRI experiment at 11.7 T. Two MRI scans, including T mapping and CEST imaging under three B amplitudes of 0.75, 1.0, and 1.5 μT, were conducted before and 2, 7, and 28 days after KA injection. Quasi-steady-state analysis was performed to reconstruct equilibrium Z spectra. Direct saturation was resolved using a multi-pool Lorentzian model and removed from Z spectra. The residual spectral signal (ΔZ) was used to construct the omega plot of (1-ΔZ)/ΔZ as a linear function of 1/ , from which K was quantified from the X-axis intercept. One-way ANOVA or two-tailed paired student's t-test was employed with P < 0.05 as statistically significant. RESULTS: All animals exhibited repetitive status epilepticus with IV to V seizure stages after KA injection. At day 28, K values in the hippocampus and cerebral cortex at the surgical hemisphere with KA injection were significantly higher than that at the time points of control and/or day 2 in the same regions (P < 0.01). Moreover, the values were significantly higher than that in respective contralateral regions at day 28 (P < 0.02). No substantial changes of K were seen in bilateral thalamus or contralateral hemisphere among time points (all P > 0.05). CONCLUSIONS: K increase significantly in the cerebral cortex and hippocampus at the surgical hemisphere, especially at day 28, likely due to substantial alterations at chronic epilepsy stage. K MRI is promising to evaluate brain impairment, facilitating the diagnosis and evaluation of neurological disorders.
Ga-pentixafor PET/CT Is a Supplementary Method for Primary Aldosteronism Subtyping Compared with Adrenal Vein Sampling.
Yi T, Lu D, Cui Y … +11 more , Zhang Z, Yang X, Zhang J, Qiu L, Weng H, Liu L, Duan X, Zhao G, Ma W, Gao Y, Fan Y
Mol Imaging Biol · 2025 Feb · PMID 39715984 · Full text
PURPOSE: To investigate the diagnostic efficacy of Ga-pentixafor positron emission tomography/computed tomography (PET/CT) in primary aldosteronism (PA) subtyping and lateralization of aldosterone secretion in PA patient...
PURPOSE: To investigate the diagnostic efficacy of Ga-pentixafor positron emission tomography/computed tomography (PET/CT) in primary aldosteronism (PA) subtyping and lateralization of aldosterone secretion in PA patients. PROCEDURES: 37 patients who were diagnosed with PA, were prospectively enrolled in the study, and underwent adrenal vein sampling (AVS) after Ga-pentixafor PET/CT was conducted. Lateralization index (LI), defined as aldosterone/cortisol ratio in the dominant side to the contralateral adrenal vein when bilateral adrenal vein catheterization succeeded, and the aldosterone/cortisol ratio in the left adrenal vein to IVC (LAV/IVC) when the catheterization of right adrenal vein failed, were applied to determine lateralization side. Statistical analysis was performed using SPSS 21.0. RESULTS: The female proportion of all patients with PA was 32.4% (12/37), and the mean age was 51.3 ± 10.9 years. Patients with bilateral adrenal mass accounted for 54.1% (20/37), and 10 of them (27.0%) had adrenal hyperplasia or adrenal nodules ≤ 1.0 cm. In all 37 patients, the sensitivity, specificity and accuracy of Ga-pentixafor PET/CT in distinguishing lateralization by visualization were 89.3%, 77.8% and 86.5%, respectively. The area under the ROC curve for detecting positive lateralization based on the value of Ga-pentixafor SUV was 0.750 (95%CI 0.578-0.922, p = 0.026). The optimum SUV cut-off value was 6.86, with the sensitivity of 78.6%, specificity of 66.7%, and accuracy of 78.4%. Defining SUV ratio as SUV/SUV of contralateral adrenal gland, the area under the ROC curve for identifying lateralization based on the SUV ratio was 0.710 (95%CI 0.500-0.921, p = 0.061). The optimum SUV ratio cut-off was 2.40, with the sensitivity of 60.7%, specificity of 88.9%, and accuracy of 67.6%. The consistency of Ga-pentixafor PET/CT with AVS was of no significant difference between patients with bilateral adrenal lesions (80.0%, 16/20) and unilateral lesion (94.1%, 16/17; p = 0.737), and no significance was revealed in the consistency between patients with adrenal hyperplasia or adrenal lesion of diameter ≤ 1 cm (81.8%, 9/11) and those with adrenal lesions > 1 cm (88.5%, 23/26; p = 0.884). CONCLUSIONS: Ga-pentixafor PET/CT showed at least 80% consistency for the lateralization in patients with PA compared with AVS, even in those presented with bilateral adrenal hyperplasia. Visual analysis exhibited better diagnostic efficacy compared with SUV or SUV/SUV of the contralateral adrenal gland.( ChiCTR2300073049. Registered 30 June 2023. Retrospectively registered).
Ga-PSMA PET/CT-Based Model Predicts Perineural Invasion of Prostate Cancer with Whole-Mount Sections.
Gao J, Fu Y, He K … +3 more , Xu Q, Wang F, Guo H
Mol Imaging Biol · 2025 Feb · PMID 39681774 · Publisher ↗
PURPOSE: To develop a novel risk model incorporating Ga-PSMA PET/CT parameters for prediction of perineural invasion (PNI) of prostate cancer (PCa). METHODS: The study retrospectively enrolled 192 PCa patients with preop...
PURPOSE: To develop a novel risk model incorporating Ga-PSMA PET/CT parameters for prediction of perineural invasion (PNI) of prostate cancer (PCa). METHODS: The study retrospectively enrolled 192 PCa patients with preoperative multiparametric MRI, Ga-PSMA PET/CT and radical specimen. Imaging parameters were derived from both mpMRI and PET/CT images. S100 immunohistochemistry staining was conducted to evaluate PNI of PCa. Significant predictors were derived with univariate and multivariate logistic regression analyses, and the PNI-risk nomogram was constructed with significant predictors. Internal discrimination validation was performed with receiver operating characteristic analysis. Calibration curves were plotted, decision curve and clinical impact curve analysis were performed for clinical benefit exploration. RESULTS: With the median peritumoral nerve density of 6, patients were stratified as low-PNI group (nerve density < 6, n = 78, 40.6%) and high-PNI group (nerve density ≥ 6, n = 114, 59.4%). Compared with low-PNI PCa, high-PNI PCa harbored significantly larger imaging lesion diameter (P < 0.001), higher PI-RADS score (P = 0.009), higher SUVmax (P < 0.001), larger tumor diameter (P = 0.024) and higher Gleason grade group (P < 0.001). Further, with univariate and multivariate analyses, imaging lesion diameter (OR 2.98, 95% CI 1.73-5.16, P = 0.004) and SUVmax (OR 3.59, 95%CI 2.32-5.55, P < 0.001) and were identified as independent predictors for PNI in PCa, and a PNI-risk nomogram incorporating these two predictors was constructed. The PNI-risk nomogram demonstrated considerable calibration (mean absolute error 0.026) and discrimination (area under the curve = 0.889, sensitivity 73.1%, specificity 97.4%) abilities, harboring net benefits with threshold probabilities range from 0 to 0.80. CONCLUSION: Ga-PSMA PET/CT-based model could effectively predict the perineural invasion of PCa. These results may help with the decision-making on active surveillance, focal therapy and surgery approach. Additionally, patients suspicious of high-density PNI PCa should receive more radical treatment than low-PNI PCa.
Ex Vivo Human Tissue Functions as a Testing Platform for the Evaluation of a Nerve-Specific Fluorophore.
Bateman LM, Streeter SS, Hebert KA … +8 more , Parker DJ, Obando K, Moreno KSS, Zanazzi GJ, Barth CW, Wang LG, Gibbs SL, Henderson ER
Mol Imaging Biol · 2025 Feb · PMID 39658767 · Full text
SIGNIFICANCE: Selecting a nerve-specific lead fluorescent agent for translation in fluorescence-guided surgery is time-consuming and expensive. Preclinical fluorescent agent studies rely primarily on animal models, which...
SIGNIFICANCE: Selecting a nerve-specific lead fluorescent agent for translation in fluorescence-guided surgery is time-consuming and expensive. Preclinical fluorescent agent studies rely primarily on animal models, which are a critical component of preclinical testing, but these models may not predict fluorophore performance in human tissues. AIM: The primary aim of this study was to evaluate and compare two preclinical models to test tissue-specific fluorophores based on discarded human tissues. The secondary aim was to use these models to determine the ability of a molecularly targeted fluorophore, LGW16-03, to label ex vivo human nerve tissues. APPROACH: Patients undergoing standard-of-care transtibial or transfemoral amputation were consented and randomized to topical or systemic administration of LGW16-03 following amputation. After probe administration, nerves and background tissues were surgically resected and imaged to determine nerve fluorescence signal-to-background tissue ratio (SBR) and signal-to-noise ratio (SNR) metrics. Analysis of variance (ANOVA) determined statistical differences in metric means between administration cohorts and background tissue groups. Receiver operating characteristic (ROC) curve-derived statistics quantified the discriminatory performance of LGW16-03 fluorescence for labeling nerve tissues. RESULTS: Tissue samples from 18 patients were analyzed. Mean nerve-to-adipose SBR was greater than nerve-to-muscle SBR (p = 0.001), but mean nerve-to-adipose SNR was not statistically different from mean nerve-to-muscle SNR (p = 0.069). Neither SBR nor SNR means were statistically different between fluorophore administration cohorts (p ≥ 0.448). When administration cohorts were combined, nerve-to-adipose SBR was greater than nerve-to-muscle SBR (mean ± standard deviation; 4.2 ± 2.9 vs. 1.8 ± 1.9; p < 0.001), but SNRs for nerve-to-adipose and nerve-to-muscle were not significantly different (5.1 ± 4.0 vs. 3.1 ± 3.4; p = 0.055). ROC curve-derived statistics to quantify LGW16-03 nerve labeling performance varied widely between patients, with sensitivities and specificities ranging from 0.2-99.9% and 0.4-100.0%. CONCLUSION: Systemic and topical administration of LGW16-03 yielded similar fluorescence labeling of nerve tissues. Both administration approaches provided nerve-specific contrast similar to that observed in preclinical animal models. Fluorescence contrast was generally higher for nerve-to-adipose versus nerve-to-muscle. Ex vivo human tissue models provide safe evaluation of fluorophores in the preclinical phase and can aid in the selection of lead agents prior to first-in-human trials.
Preclinical and Clinical-Scale Magnetic Particle Imaging of Natural Killer Cells: in vitro and ex vivo Demonstration of Cellular Sensitivity, Resolution, and Quantification.
Sehl OC, Yang Y, Anjier AR … +16 more , Nevozhay D, Cheng D, Guo K, Fellows B, Mohtasebzadeh AR, Mason EE, Sanders T, Kim P, Trease D, Koul D, Goodwill PW, Sokolov K, Wintermark M, Gordon N, Greve JM, Gopalakrishnan V
Mol Imaging Biol · 2025 Feb · PMID 39653984 · Full text
PURPOSE: Clinical adoption of NK cell immunotherapy is underway for medulloblastoma and osteosarcoma, however there is currently little feedback on cell fate after administration. We propose magnetic particle imaging (MP...
PURPOSE: Clinical adoption of NK cell immunotherapy is underway for medulloblastoma and osteosarcoma, however there is currently little feedback on cell fate after administration. We propose magnetic particle imaging (MPI) may have applications for the quantitative detection of NK cells. PROCEDURES: Human-derived NK-92 cells were labeled by co-incubation with iron oxide nanoparticles (VivoTrax™) for 24 h then excess nanoparticles were washed with centrifugation. Cytolytic activity of labeled versus unlabeled NK-92 cells was assessed after 4 h of co-incubation with medulloblastoma cells (DAOY) or osteosarcoma cells (LM7 or OS17). Labeled NK-92 cells at two different doses (0.5 or 1 × 10) were administered to excised mouse brains (cerebellum), fibulas, and lungs then imaged by 3D preclinical MPI (MOMENTUM™) for detection relative to fiducial markers. NK-92 cells were also imaged by clinical-scale MPI under development at Magnetic Insight Inc. RESULTS: NK-92 cells were labeled with an average of 3.17 pg Fe/cell with no measurable effects on cell viability or cytolytic activity against 3 tumor cell lines. MPI signal was directly quantitative with the number of labeled NK-92 cells, with preclinical limit of detection of 3.1 × 10 cells on MOMENTUM imager. Labeled NK-92 cells could be accurately localized in mouse brains, fibulas, and lungs within < 1 mm of stereotactic injection coordinates with preclinical scanner. Feasibility for detection on a clinical-scale MPI scanner was demonstrated using 4 × 10 labeled NK-92 cells, which is in the range of NK cell doses administered in our previous clinical trial. CONCLUSION: MPI can provide sensitive, quantitative, and accurate spatial information on NK cells soon after delivery, showing initial promise to address a significant unmet clinical need to track NK cell fate in patients.
In Vivo Mouse Abdominal Oxygen Imaging And Assessment of Subcutaneously Implanted Beta Cell Replacement Devices.
Canavesi I, Viswakarma N, Epel B … +1 more , Kotecha M
Mol Imaging Biol · 2025 Feb · PMID 39633071 · Publisher ↗
PURPOSE: Type 1 diabetes (T1D) is an autoimmune disease that leads to the loss of insulin-producing pancreatic beta cells. Beta cell replacement devices or bioartificial pancreas (BAP) have shown promise in curing T1D an...
PURPOSE: Type 1 diabetes (T1D) is an autoimmune disease that leads to the loss of insulin-producing pancreatic beta cells. Beta cell replacement devices or bioartificial pancreas (BAP) have shown promise in curing T1D and providing long-term insulin independence without the need for immunosuppressants. Hypoxia in BAP devices damages cells and imposes limitations on device dimensions. Noninvasive in vivo oxygen imaging assessment of implanted BAP devices will provide the necessary feedback and improve the chances of success. Pulse-mode electron paramagnetic resonance (EPR) oxygen imaging (EPROI) using injectable trityl OX071 as the oxygen-sensitive agent is an excellent technique for obtaining partial oxygen pressure (pO) maps in vitro and in vivo. In this study, our goal was to optimize in vivo mouse abdominal EPROI and demonstrate proof-of-concept pO imaging of subcutaneously implanted BAP devices. METHODS: All EPROI experiments were performed using a 25 mT EPROI instrument, JIVA-25®. For in vivo EPROI experiments, trityl OX071, a whole-body mouse resonator (∅32 mm × 35 mm), C57BL6 mice, and the inversion recovery electron spin echo (IRESE) pulse sequence were utilized. We investigated the signal amplitude and pO in mouse abdomen region for intravenous (i.v.) and intraperitoneal (i.p.) injection methods with either only a single bolus (B) or bolus plus infusion (BI) for 72.2 mM OX071 and the effect of OX071 concentrations from 18 to 72.2 mM for the i.p.-B injection method. We also investigated the impact of animal respiratory rate on mouse abdominal pO. Finally, we performed proof-of-concept pO imaging of two subcutaneously implanted BAP devices, OxySite and TheraCyte. At the end of the four-week study, the TheraCyte devices were extracted and analyzed for fibrosis, vascular differentiation, and immune cell infiltration. RESULTS: We established that mouse abdominal pO remains stable irrespective of trityl injection methods, concentrations, imaging time, or animal breathing rate. We demonstrate that the i.p.-B and i.p.-BI methods are suitable for EPROI, and i.p.-B method provides higher signal amplitude compared to i.v.-BI and up to 75 min of imaging. An injection with a reduced trityl concentration and higher volume provides higher signal amplitude for i.p.-B method at the beginning. We also highlight the advantage of milder anesthesia for consistent, reliable mouse pO imaging. Finally, we demonstrate that EPROI could provide longitudinal noninvasive oxygen assessment of subcutaneously implanted BAP devices in vivo. CONCLUSIONS: In vivo EPROI is a reliable technique for mouse abdominal oxygen imaging and longitudinal assessment of subcutaneously implanted BAP devices noninvasively. This work reports abdominal oxygen imaging in the mouse model and demonstrates its application for the assessment of BAP devices. Even though the application focus of this work was on cell therapy, the techniques developed will have a much broader use in the biomedical field.
First-in-human Evaluation of Safety and Dosimetry of [Cu]FBP8: A fibrin-binding PET Probe.
Izquierdo-Garcia D, Désogère P, Philip AL … +3 more , Sosnovik DE, Catana C, Caravan P
Mol Imaging Biol · 2025 Feb · PMID 39633070 · Publisher ↗
PURPOSE: This study presents for the first time in humans the biodistribution, clearance and dosimetry estimates of [Cu]Fibrin Binding Probe #8 ([Cu]FBP8) in healthy subjects. [Cu]FBP8-PET previously demonstrated its pot...
PURPOSE: This study presents for the first time in humans the biodistribution, clearance and dosimetry estimates of [Cu]Fibrin Binding Probe #8 ([Cu]FBP8) in healthy subjects. [Cu]FBP8-PET previously demonstrated its potential in two recent applications: thrombus imaging and pulmonary fibrosis. PROCEDURES: This prospective study included 8 healthy subjects to evaluate biodistribution, safety and dosimetry estimates of [Cu]FBP8, a fibrin-binding positron emission tomography (PET) probe. All subjects underwent up to 3 sessions of PET/Magnetic Resonance Imaging (PET/MRI) 0-2 h, 4 h and 24 h post injection. Dosimetry estimates were obtained using OLINDA 2.2 software. RESULTS: Subjects were injected with 400 MBq of [Cu]FBP8. Subjects did not experience adverse effects due to the injection of the probe. [Cu]FBP8 PET images demonstrated fast blood clearance (half-life = 67 min) and renal excretion of the probe, showing low background signal across the body. The organs with the higher doses were: the urinary bladder (0.075 vs. 0.091 mGy/MBq for males and females, respectively); the kidneys (0.050 vs. 0.056 mGy/MBq respectively); and the liver (0.027 vs. 0.035 mGy/MBq respectively). The combined mean effective dose for males and females was 0.016 ± 0.0029 mSv/MBq, lower than the widely used [F]fluorodeoxyglucose ([F]FDG, 0.020mSv/MBq). CONCLUSIONS: This study demonstrates the following properties of the [Cu]FBP8 probe: low dosimetry estimates; fast blood clearance and renal excretion; low background signal; and whole-body acquisition within 20 min in a single session. These properties provide the basis for [Cu]FBP8 to be an excellent candidate for whole-body non-invasive imaging of fibrin, an important driver/feature in many cardiovascular, oncological and neurological conditions.
The Potential Utility of (2S,4R)-4-[F]fluoroglutamine as a Novel Metabolic Imaging Marker for Inflammation Explored by Rat Models of Arthritis and Paw Edema.
Kim MJ, Akula HK, Marden J … +4 more , Li K, Hu B, Vaska P, Qu W
Mol Imaging Biol · 2025 Feb · PMID 39572469 · Publisher ↗
PURPOSE: (2S,4R)-4-[F]fluoroglutamine ([F]FGln) is a promising metabolic imaging marker in cancer. Based on the fact that major inflammatory cells are heavily dependent on glutamine metabolism like cancer cells, we explo...
PURPOSE: (2S,4R)-4-[F]fluoroglutamine ([F]FGln) is a promising metabolic imaging marker in cancer. Based on the fact that major inflammatory cells are heavily dependent on glutamine metabolism like cancer cells, we explored the potential utility of [F]FGln as a metabolic imaging marker for inflammation in two rat models: carrageenan-induced paw edema (CIPE) and collagen-induced arthritis (CIA). PROCEDURES: The CIPE model (n = 4) was generated by injecting 200 µL of 3% carrageenan solution into the left hind paw three hours before the PET. The CIA model (n = 4) was generated by injecting 200 µg of collagen emulsion subcutaneously at the tail base 3-4 weeks before the PET. A qualitative scoring system was used to assess the severity of paw inflammation. After a CT scan, 15.7 ± 4.9 MBq of [F]FGln was injected via the tail vein, followed by a dynamic micro-PET scan for 90 min under anesthesia with isoflurane. The standard uptake value of [F]FGln was measured by placing a volume of interest in each paw. The non-injected right hind paws of the CIPE model rats served as controls for both models. The paws with CIA were pathologically examined after PET. RESULTS: The CIPE models showed a trend toward higher uptake in the injected paw compared to the non-injected paw (P = 0.068). In CIA models, uptake in the paws with severe inflammation was significantly higher than the controls (P = 0.011), while that with mild and no inflammation was slightly higher (33%) and lower (-7%), respectively. Combined overall, the [F]FGln uptake in CIA showed a significant positive correlation with inflammation severity (r = 0.88, P = 0.009). The pathological findings confirmed profound inflammation in CIA. CONCLUSIONS: [F]FGln uptake was increased in both acute and chronic inflammation, and the uptake level was significantly correlated with the severity, suggesting its potential utility as a novel metabolic imaging marker for inflammation.
Quantitative Imaging of Regional Cerebral Protein Synthesis in Clinical Alzheimer's Disease by [C]Leucine PET.
Herholz K, McMahon A, Thompson JC … +5 more , Jones M, Boutin H, Gregory J, Parker CA, Hinz R
Mol Imaging Biol · 2024 Dec · PMID 39567463 · Full text
PURPOSE: Protein synthesis is essential to maintain integrity and function of the human brain, and protein synthesis is associated specifically with the formation of long-term memory. Experimental and clinical observatio...
PURPOSE: Protein synthesis is essential to maintain integrity and function of the human brain, and protein synthesis is associated specifically with the formation of long-term memory. Experimental and clinical observations indicate that this process is disturbed in Alzheimer's dementia and other neurodegenerative diseases. In-vivo investigation with positron emission tomography (PET) using [C]leucine provides a unique possibility to measure regional cerebral protein synthesis (rCPS) rates in human brain and to determine whether it is altered in Alzheimer's disease (AD), and thus may provide a target for future therapeutic interventions. PROCEDURES: In this first human study, we measured rCPS by [C]leucine PET in four patients with AD (age 57-73 years) and compared the results with six healthy controls (three of whom were age matched and the other three were young controls). Quantification of rCPS also required measurement of amino acid (AA) levels and of free and protein-bound [C]leucine in plasma during the 90 min PET scans conducted following at least six hours of fasting. RESULTS: Rates of rCPS measured in absolute units of nmol/g/min ranged between 1.81 and 2.53 in AD patients, 2.10 and 2.54 in matched controls, and 2.21 to 2.35 in the young controls. Mean and median values did not show significant differences between the groups. Rates of rCPS also depended upon whether corrections for plasma AA levels were included in the calculations. When considering regional values relative to the corpus callosum as a reference region, there was a tendency towards impairment of rCPS in patients, which was most prominent in the parietal cortex, but did not reach significance. Similar findings were observed with normalisation of rCPS to global cortical mean. CONCLUSIONS: In summary, this first human study assessing regional protein synthesis with [C]leucine in AD has demonstrated where the sources of variance in measurements of cerebral protein synthesis may arise, along with the potential magnitude of this variance. This study also indicates that there is a tendency towards impairment of rCPS in patients with Alzheimer's disease, which requires further investigation including possible partial volume effects due to atrophy.
Effects of Neoadjuvant Therapy on Tumour Target Expression of Oesophageal Cancer Tissue for NIR Fluorescence Imaging.
Galema HA, Neijenhuis LKA, Lauwerends LJ … +13 more , Dekker-Ensink NG, Verhoef C, Vahrmeijer AL, Bhairosingh SS, Kuppen PJK, Rogalla S, Burggraaf J, Lagarde SM, Wijnhoven BPL, Hutteman M, Doukas M, Keereweer S, Hilling DE
Mol Imaging Biol · 2024 Dec · PMID 39562416 · Publisher ↗
PURPOSE: Oesophaegal cancer patients with a clinical complete response (CR) after neoadjuvant chemoradiotherapy (nCRT) are candidates for an active surveillance strategy. Regrowth rates of 40% after initial clinical CR i...
PURPOSE: Oesophaegal cancer patients with a clinical complete response (CR) after neoadjuvant chemoradiotherapy (nCRT) are candidates for an active surveillance strategy. Regrowth rates of 40% after initial clinical CR indicate that identification of a true complete response to nCRT remains challenging. Near-infrared tumour-specific fluorescence endoscopic imaging might help to discriminate patients with a true complete response from patients with residual disease. This study aims to find potential markers to enable molecular imaging in oesophageal cancer and to assess the effect of nCRT on marker expression. PROCEDURES: Oesophageal cancer tissue slides of diagnostic biopsies (n = 41) (pre-treatment) and paired surgical specimens (n = 31) (post-treatment) were collected. Tissue slides of patients with adenocarcinoma (n = 29) and squamous cell carcinoma (n = 12)) were included. Immunohistochemistry was performed to assess expression of the tumour markers CEA, EpCAM, VEGF-α, EGFR, and c-MET in the tumour and compared to the expression of these markers in surrounding healthy tissue. A total immunostaining score (TIS, range 0-12), which combines the percentage and intensity of stained cells, was calculated. The TIS of pre-treated biopsies were compared with the TIS of the post-treatment surgical specimens to assess the effect of neoadjuvant therapy on the marker expression. RESULTS: The median TIS of EpCAM in adenocarcinomas was 10, vs. 0 in healthy mucosa (p < 0.001). The median TIS of EGFR in squamous cell carcinoma was 12, vs. 4 in healthy mucosa (p < 0.001). Neoadjuvant therapy did not affect the expression of the markers. CONCLUSION: EpCAM and EGFR appear to be the most suitable targets for tumour-specific NIR fluorescence imaging of oesophageal adenocarcinoma and squamous cell carcinoma, respectively. Unaffected expression of all suitable markers by neoadjuvant therapy implies that the diagnostic biopsy can be used to select a patient-specific target for response evaluation by molecular imaging.
Using GeoMx DSP Spatial Proteomics to Investigate Immune Infiltration of NOD Mouse Islet and Exocrine Compartments.
Tekin H, Lindhardt C, Antvorskov JC … +6 more , Bager NS, Michaelsen SR, Areškevičiūtė A, Vind JP, Kristensen BW, Josefsen K
Mol Imaging Biol · 2024 Dec · PMID 39557779 · Full text
PURPOSE: Type 1 Diabetes (T1D) pathogenesis involves immune cells infiltrating pancreatic Islets of Langerhans, leading to T cell activation, beta cell destruction, and impaired insulin production. However, infiltration...
PURPOSE: Type 1 Diabetes (T1D) pathogenesis involves immune cells infiltrating pancreatic Islets of Langerhans, leading to T cell activation, beta cell destruction, and impaired insulin production. However, infiltration has a heterogenic nature that isn't described in detail, as not all islets are infiltrated. The aim of this study was to investigate if the observed heterogeneity is coupled to differences in immune and/or dysfunctional status of islets or exocrine cells, and if specific markers could elucidate mechanistic details of T1D pathogenesis. PROCEDURES: The GeoMx platform was used to spatially quantify protein levels in pancreatic islets and exocrine tissue in Non-Obese Diabetic (NOD) mice. The protein panel included 17 immune activity markers and nine dysfunction markers. Immunohistochemical (IHC) staining and digital image analysis was used to analyze select marker proteins. RESULTS: Use of the GeoMx platform to investigate T1D was shown to be possible, as Granzyme B protein levels were found to be lower in distal islet areas when compared to proximal areas. Smooth Muscle Actin protein levels were higher in exocrine areas proximal to immune-infiltrated islets, when compared to distally located exocrine areas. Findings from GeoMx were however not observed in IHC-stained sections. CONCLUSIONS: This study demonstrates that investigating T1D is possible with spatial proteomics, as the assays revealed presence of heterogenic islet areas in NOD mice, which may play a role in T1D progression and escape from immune recognition. This study highlights the potential of spatial technologies for elucidating T1D pathogenesis and future treatment strategies.
Thymidine Phosphorylase Imaging Probe for Differential Diagnosis of Metabolic dysfunction-associated Steatohepatitis.
Higashikawa K, Uehara R, Horiguchi S … +7 more , Shibata Y, Okubo N, Mizuno Y, Yasui H, Ohnishi S, Takeda H, Kuge Y
Mol Imaging Biol · 2024 Dec · PMID 39538096 · Publisher ↗
PURPOSE: Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises simple steatosis (SS), which has a low risk of mortality, and metabolic dysfunction-associated steatohepatitis (MASH), which can progres...
PURPOSE: Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises simple steatosis (SS), which has a low risk of mortality, and metabolic dysfunction-associated steatohepatitis (MASH), which can progress to liver cirrhosis and hepatocellular carcinoma. Because differentiation between MASH and SS is the most important issue in the diagnosis of MASLD, the establishment of noninvasive diagnostic methods is urgently needed. In this study, we evaluated the potential of [I]IIMU, a thymidine phosphorylase (TYMP) targeted SPECT imaging probe, for differential diagnosis of MASLD in a preclinical animal model. PROCEDURES: SS and MASH mice were prepared by feeding db/db mice with a standard diet and a methionine/choline-deficient diet, respectively. Control mice were prepared by feeding m/m mice with a standard diet. TYMP expression in the liver was evaluated by RT-PCR, western blotting, and immunohistochemistry. The biodistribution of [I]IIMU in the three model mice was evaluated at 30 min post-injection. SPECT/CT imaging studies of the three model mice were performed 30 min after injection of [I]IIMU. RESULTS: Hepatic TYMP expression level was the highest in the SS mice and the lowest in the MASH mice at both mRNA and protein levels. The immunohistochemistry experiment showed a patchy distribution of TYMP only in the liver of MASH mice. In the biodistribution study, the hepatic accumulation of [I]IIMU was the highest in the SS mice and the lowest in the MASH mice. The SPECT/CT imaging study showed similar results to the biodistribution experiment. CONCLUSION: Hepatic TYMP expression level may serve as a promising imaging biomarker for differential diagnosis of SS and MASH. SPECT imaging using [I]IIMU potentially provides a novel noninvasive diagnostic method to differentiate MASH and SS.
Evaluations of a Cutaneous Wound Healing Model Using Oxygen Enhanced - Dynamic Contrast Enhanced Photoacoustic Imaging (OE-DCE PAI).
Yang E, Khaled A, Liang X … +4 more , de la Cerda J, Schuler FW, Goel S, Pagel MD
Mol Imaging Biol · 2024 Dec · PMID 39532769 · Full text
PURPOSE: Preclinical models of cutaneous wound healing can be useful for improving clinical wound care. Oxygen Enhanced Photoacoustic imaging (OE PAI) can measure oxygenation, and Dynamic Contrast Enhanced (DCE) PAI can...
PURPOSE: Preclinical models of cutaneous wound healing can be useful for improving clinical wound care. Oxygen Enhanced Photoacoustic imaging (OE PAI) can measure oxygenation, and Dynamic Contrast Enhanced (DCE) PAI can measure vascular perfusion. We investigated how a combined OE-DCE PAI protocol can measure vascular oxygenation and perfusion to a cutaneous healing model. PROCEDURES: We developed a cutaneous "punch" wound model and photographed the wounds to track healing for 9 days. We performed OE-DCE PAI on Day 0, 3, 6, and 9. OE PAI was performed with 21% O and 100% O breathing gases to measure oxyhemoglobin (HbO), deoxyhemoglobin (Hb), total hemoglobin (HbT), and oxygen saturation (%sO), along with changes in these parameters caused by a change in breathing gas (ΔHb, ΔHbO, ΔHbT, ΔsO). To perform DCE PAI, indocyanine green (ICG) was administered intravenously while monitoring the PAI signal for 10 min as the agent washed through the wound area, which was used to evaluate the wash-out rate. RESULTS: The average wound size was significantly smaller only by Day 6. For comparison, OE PAI measured a significant increase in HbO, Hb, HbT, and %sO immediately after creating the wound, which significantly decreased by Day 3 and continued to decrease towards values for normal tissue by Day 9. The vascular wash-out rate significantly increased by Day 3, and continued to increase during the healing process. Notably, the wash-out rate can be assessed at a single PAI absorbance wavelength and by simply comparing signal amplitudes without advanced analysis, which may facilitate clinical translation. CONCLUSIONS: OE-DCE PAI can monitor significant changes in vascular perfusion and oxygenation prior to significant changes in cutaneous wound size. These results establish OE-DCE PAI as a tool for future pre-clinical wound healing studies and eventual clinical translation.
Optimisation of Animal Handing and Timing of 2-deoxy-2-[F]fluoro-D-glucose PET Tumour Imaging in Mice.
Hesketh RL, Lewis DY, Brindle KM
Mol Imaging Biol · 2024 Dec · PMID 39528890 · Full text
PURPOSE: In humans, 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) tumour-to-background contrast continues to increase long after a typical uptake period of 45 - 60 min. Similar studies have not been performed in mice and the st...
PURPOSE: In humans, 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) tumour-to-background contrast continues to increase long after a typical uptake period of 45 - 60 min. Similar studies have not been performed in mice and the static imaging time point for most studies is arbitrarily set at 30 - 60 min post-injection of [F]FDG. Ideally, static PET imaging should be performed after the initial period of rapid uptake but this period has not been defined in mice, with previous dynamic studies in mice being limited to 60 min. This study aimed to define the kinetics of [F]FDG biodistribution over periods of 3 - 4 h in different murine tumour models, both subcutaneous and autochthonous, and to further refine fasting and warming protocols used prior to imaging. PROCEDURES: Dynamic [F]FDG PET-CT scans lasting 3 or 4 h were performed with C57BL/6 J and Balb/c nude mice bearing subcutaneous EL4 murine T-cell lymphoma and Colo205 human colorectal tumours, respectively, and with transgenic Eμ-Myc lymphoma mice. Prior to [F]FDG injection, four combinations of different animal handling conditions were used: warming for 1 h at 31 °C; maintenance at room temperature (20 - 24 °C), fasting for 6 - 10 h and a fed state. RESULTS: Tumour mean standardised uptake value (SUV) peaked at 147 ± 48 min post injection in subcutaneous tumours and 74 ± 31 min in autochthonous Eμ-Myc lymphomas. The tumour-to-blood ratio (TBR) peaked at 171 ± 57 and 83 ± 33 min in subcutaneous and autochthonous Eμ-Myc tumours, respectively. Fasting increased tumour [F]FDG uptake and suppressed myocardial uptake in EL4 tumour-bearing mice. There was a good correlation between tumour SUV and K calculated using an input function (IDIF) derived from the inferior vena cava. CONCLUSIONS: Delayed static [F]FDG-PET imaging (> 60 min) in both autochthonous and subcutaneous tumours in improved tumour-to-background contrast and increased reproducibility.
Comparison Between Prone SPECT-Based Semi-Quantitative Parameters and MBI-Based Semi-Quantitative Parameters in Patients with Locally Advanced Breast Cancer.
van de Burgt A, van Velden FHP, Corion CLS … +5 more , Collarino A, Olmos RAV, Smit F, de Geus-Oei LF, Arias-Bouda LMP
Mol Imaging Biol · 2024 Dec · PMID 39516430 · Full text
PURPOSE: This study evaluates the semi-quantitative single-photon emission computed tomography (SPECT) parameters of prone SPECT using [Tc]Tc-sestamibi and compares them with Molecular Breast Imaging (MBI)-derived semi-q...
PURPOSE: This study evaluates the semi-quantitative single-photon emission computed tomography (SPECT) parameters of prone SPECT using [Tc]Tc-sestamibi and compares them with Molecular Breast Imaging (MBI)-derived semi-quantitative parameters for the potential use of response prediction in women with locally advanced breast cancer (LABC). PROCEDURES: Patients with proven LABC with a tumor ≥ 2 cm on mammography and an indication for MBI using [Tc]Tc-sestamibi were prospectively enrolled. All patients underwent a prone SPECT/CT at 5 min (early exam) and an additional scan at 90 min (delayed exam) after injection of 600 MBq [Tc]Tc-sestamibi to compose wash-out rates (WOR). All patients underwent MBI after early SPECT/CT. Volumes of interest of the primary tumor were drawn semi-automatically on early and delayed SPECT images. Semi-quantitative analysis included maximum and mean standardized uptake values (SUV, SUV,), functional tumor volume (FTV), total lesion mitochondrial uptake (TLMU), tumor-to-background ratios (TBRand TBR), WOR and coefficient of variation (COV). Subsequently, the FTV, TBR and COV were compared to FTV, TBR and COV. RESULTS: Eighteen patients were included. Early SUV and TBR showed significantly higher interquartile range (IQR) compared to SUV and TBR, respectively 2.22 (2.33) g/mL, 6.86 (8.69), 1.29 (1.39) g/mL and 3.99 (5.07) (median (IQR), p < 0.05). WOR showed a large IQR (62.28), indicating that there is WOR variation among the LABC patients. FTV showed no difference between MBI and early SPECT semi-quantitative parameter (p = 0.46). CONCLUSIONS: In LABC patients it is feasible to obtain semi-quantitative parameters from prone SPECT/CT. The FTV derived from early prone SPECT/CT is comparable with MBI-based FTV. Studies with comprehensive clinical parameters are needed to establish the clinical relevance of these semi-quantitative parameters, including WOR, for response prediction before its use in clinical routine.
In Vivo Detection of Lymph Nodes Metastasis of ESCC Using CXCR4-Targeted Tracer [Cu]Cu-NOTA-CP01.
Peng T, Li Z, Gao J … +7 more , Yang M, Qiu Y, Xian J, Bi L, Ye P, Liu Y, Jin H
Mol Imaging Biol · 2024 Dec · PMID 39497002 · Publisher ↗
PURPOSE: Esophageal squamous cell carcinoma (ESCC) frequently exhibits skip metastasis to lymph nodes; however, non-invasive imaging techniques capable of directly visualizing metastatic lymph nodes (MLN) are still lacki...
PURPOSE: Esophageal squamous cell carcinoma (ESCC) frequently exhibits skip metastasis to lymph nodes; however, non-invasive imaging techniques capable of directly visualizing metastatic lymph nodes (MLN) are still lacking. Although biopsy is the clinical standard method, it is invasive and poses risks to patient health. This study aims to detect MLN in an intralymphatic tumor metastasis model of ESCC using the CXCR4-targeted tracer [Cu]Cu-NOTA-CP01. PROCEDURES: The CXCR4 expression in ESCC cell lines was assessed using Western blot and immunofluorescence. An intralymphatic tumor metastasis model was established and monitored using bioluminescence imaging (BLI). Small animal PET studies and biodistribution studies were performed to evaluate the specificity of [Cu]Cu-NOTA-CP01 for MLN. Histopathology evaluation was employed to check for the presence of metastatic tumor cells and to assess CXCR4 expression levels in the metastatic lymph nodes. RESULTS: The intralymphatic tumor metastasis model was successfully established using the EC109/Luc cell line, which exhibited high CXCR4 expression, as verified by BLI. PET/CT imaging showed that the MLN uptakes in the baseline group were significantly inhibited in the blocking group. The ratios of MLN/muscle and MLN/blood were also significantly higher in the baseline group than in the blocking group. Ex vivo PET/CT imaging of MLN corroborated the in vivo data. Biodistribution studies further supported the PET imaging studies, showing rapid clearance of the tracer from the blood and major organs, with significantly higher MLN/muscle and MLN/blood ratios in the baseline group compared to the blocking group. Histopathological staining verified positive CXCR4 expression in these lymph nodes containing metastatic tumor cells. CONCLUSIONS: Targeting CXCR4 with [Cu]Cu-NOTA-CP01 for PET imaging of lymph nodes metastasis represents a promising approach that warrants further investigation. These findings have the potential to enhance diagnostic and therapeutic strategies for individuals with lymph nodes metastasis of ESCC.
Differentiation Between Responders and Non-Responders to Antibiotic Treatment in Mice Using F-Fluorodeoxysorbitol/PET.
Li J, Zheng H, Olson J … +2 more , Warawa JM, Ng CK
Mol Imaging Biol · 2024 Dec · PMID 39407054 · Publisher ↗
PURPOSE: Bacterial infection causes significant mortality and morbidity worldwide despite the availability of antibiotics. Differentiation between responders and non-responders early on during antibiotic treatment will b...
PURPOSE: Bacterial infection causes significant mortality and morbidity worldwide despite the availability of antibiotics. Differentiation between responders and non-responders early on during antibiotic treatment will be informative to patients and healthcare providers. Our objective was to investigate whether PET imaging with F-Fluorodeoxysorbitol (F-FDS) or F-FDG can be used to differentiate responders from non-responders to antibiotic treatment. PROCEDURES: NTUH-K2044 was used for infection in Albino C57 female mice. Each mouse was inoculated intratracheally with NTUH-K2044 to induce lung infection (n = 8). For treatment studies, two bacterial doses for animal inoculation and two treatment starting times were compared to optimize treatment profiles. F-FDS or F-FDG /PET imaging was performed to monitor treatment progression. RESULTS: Our results demonstrated that the treatment profiles for mice infected with 25 CFU hvKp and antibiotic treatment starting at 24 p.i. were not ideal due to no evidence of lung infection and lack of treatment efficacy. The optimal scheme is to use 250 CUF for infection and start antibiotic treatment at 24 h p.i. to monitor antimicrobial efficacy. 75% of the mice were classified as responders to antibiotic treatment. 25% of the mice were classified as non-responders. F-FDG was used to compare with F-FDS, but all mice showed increased lung uptake of F-FDG during 3-day treatments. CONCLUSIONS: F-FDS is a promising PET tracer to image bacterial infection. It can be used to monitor response to treatment, and differentiate responders from non-responders to antibiotic treatment, but F-FDG cannot, probably due to the presence of high degree of inflammation before and after treatment.
2023 World Molecular Imaging Congress Program.
Mol Imaging Biol · 2025 Jan · PMID 39402408 · Publisher ↗
Abstract loading — click title to view on PubMed.
Utility of Quantitative Assessment of Tc-99m-diethylenetriamine-penta-acetic acid-galactosyl Human Serum Albumin SPECT/CT in the Identification of Severe Liver Fibrosis: Its Complementary Diagnostic Value with Other Liver Function Indices.
Kozaki Y, Ichikawa Y, Nakamura S … +6 more , Kobayashi T, Tomita Y, Nagata M, Kuriyama N, Mizuno S, Sakuma H
Mol Imaging Biol · 2024 Dec · PMID 39390273 · Publisher ↗
PURPOSE: To evaluate the value of Tc-99m-diethylenetriamine-penta-acetic acid-galactosyl human serum albumin (Tc-GSA) single photon emission computed tomography (SPECT) for assessing liver fibrosis, and to assess its com...
PURPOSE: To evaluate the value of Tc-99m-diethylenetriamine-penta-acetic acid-galactosyl human serum albumin (Tc-GSA) single photon emission computed tomography (SPECT) for assessing liver fibrosis, and to assess its complementary value to other liver function indices such as fibrosis-4 (FIB-4) index and indocyanine green (ICG) clearance test parameters (ICG-R15 and ICG-K). PROCEDURES: Seventy-eight patients with chronic liver disease and hepatocellular carcinoma who underwent Tc-GSA scintigraphy and other liver function tests including ICG test and FIB-4 index prior to hepatectomy were studied. Tc-GSA imaging was performed with SPECT/CT scanner (Discovery NM/CT 670). Immediately after injection of Tc-GSA, dynamic imaging was performed for 20 min, followed by SPECT data acquisition for 6 min. LHL15 which is a conventional index by Tc-GSA planar images, and liver uptake ration (LUR) was measured from Tc-GSA SPECT images. From the liver resection specimens, the degree of liver fibrosis was graded according to the Ludwig scale (F0-4). RESULTS: Significant differences in LUR, LHL15, ICG-R15, ICG-K, platelet count and FIB-4 index were found between the F0-3 and F4 liver fibrosis patient groups (P < 0.05). Multivariate logistic regression analysis revealed that LUR and ICG-K were independent factors for identifying severe liver fibrosis (F4). Area under the curve of receiver operating curve analysis for the logistic regression model using LUR and ICG-K was 0.83. In the patient group with higher FIB-4 (≥ 3.16), the diagnostic performance of LUR for detecting severe liver fibrosis was significantly better than LHL15 (AUC: 0.83 vs. 0.75, P = 0.048). In the high FIB-4 index group, the sensitivity and specificity for identifying F4 was 88% and 85%, respectively, with LUR cutoff value of 41.2%. CONCLUSIONS: LUR, measured by Tc-GSA SPECT, is a useful indicator for identifying sever liver fibrosis. Particularly in patients with high FIB-4 index (≥ 3.16), LUR can be a valuable indicator to identify severe liver fibrosis with high diagnostic accuracy.
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