Mol Imaging Biol [JOURNAL]
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200 papers
Integrative Analysis of F-FDG PET Radiomics and mRNA Expression in Recurrent/Metastatic Oral Squamous Cell Carcinoma: A Cross-Sectional Study.
Kim M, Gu W, Iwakawa RK … +7 more , Kina S, Nakajima T, Higuchi T, Ogawa M, Suzuki K, Tsushima Y, Yokoo S
Mol Imaging Biol · 2025 Jun · PMID 40369386 · Full text
BACKGROUND: This study explored the relationship between mRNA expression profiles obtained through next-generation sequencing (NGS) and F-fluorodeoxyglucose positron emission tomography (F-FDG PET) texture analysis in pa...
BACKGROUND: This study explored the relationship between mRNA expression profiles obtained through next-generation sequencing (NGS) and F-fluorodeoxyglucose positron emission tomography (F-FDG PET) texture analysis in patients with treatment-resistant oral squamous cell carcinoma (OSCC) who were treated with molecular-targeted drugs. We analyzed the correlation between F-FDG PET texture features and NGS data in a small cohort of five patients with recurrent or metastatic OSCC who received molecular-targeted drugs after surgery. Patients were categorized into two groups based on treatment response: responders (n = 3) and non-responders (n = 2). To validate our findings, we examined transcriptomic data from 292 OSCC patients in The Cancer Genome Atlas (TCGA) database. RESULTS: The gene ankyrin repeat and SOCS box containing two (ASB2) was significantly overexpressed in non-responders and strongly correlated with specific PET radiomic features, including GLRLM_GLNU, GLRLM_RLNU, and GLZLM_GLNU (p < 0.05). High ASB2 expression was also associated with poor prognosis in OSCC patients (p < 0.05) and decreased overall survival, as shown by Kaplan-Meier analysis of the TCGA database (p = 0.017). CONCLUSIONS: Integrating ASB2 expression data with F-FDG PET texture features could potentially improve the prediction of treatment outcomes in treatment-resistant OSCC patients undergoing molecular-targeted therapy.
[18 F]-Fluoroestradiol PET (FES-PET) and [18 F] Flurodeoxyglucose PET (FDG-PET) Imaging May Aid in Managing Therapy in Patients with Metastatic Lobular Breast Cancer.
Manohar PM, Peterson LM, Jenkins IC … +10 more , Wu QV, Kurland BF, Novakova-Jiresova A, Muzi M, Chen DL, Specht JM, Dintzis S, Kinahan PE, Mankoff DA, Linden HM
Mol Imaging Biol · 2025 Jun · PMID 40369385 · Full text
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 e...
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.
Impact of Mechanical Ventilation and Anesthesia on PET Tracer Kinetics for Combined PET/fMRI Studies in Rats.
Ma Y, Kuebler L, Haas S … +2 more , Maurer A, Herfert K
Mol Imaging Biol · 2025 Jun · PMID 40369384 · Full text
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 recor...
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 [C]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.
Attenuation Estimation and Acoustic Characterization of Mouse Lymph Node Tumor Using High-frequency Ultrasound.
Omura M, Maeda K, Tamura K … +4 more , Yoshida K, Sukhbaatar A, Kodama T, Yamaguchi T
Mol Imaging Biol · 2025 Jun · PMID 40355617 · Full text
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 operat...
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.
Radiomic Analysis of Striatal [F]FDOPA PET Imaging in Patients with Psychosis for the Identification of Antipsychotic Response.
Schiulaz A, Nordio G, Giacomel A … +9 more , Easmin R, Bettinelli A, Selvaggi P, Williams S, Turkheimer F, Jauhar S, Howes O, Veronese M, FDOPA PET Imaging Working Group
Mol Imaging Biol · 2025 Jun · PMID 40323469 · Full text
PURPOSE: Schizophrenia (SCZ) is a severe psychiatric disorder marked by abnormal dopamine synthesis, measurable through [F]FDOPA PET imaging. This imaging technique has been proposed as a biomarker for treatment stratifi...
PURPOSE: Schizophrenia (SCZ) is a severe psychiatric disorder marked by abnormal dopamine synthesis, measurable through [F]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 [F]FDOPA PET data to examine dopamine synthesis in SCZ and predict antipsychotic response. METHODS: We analysed 273 [F]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 [F]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.
The Imaging Value of F-FAPI PET/CT in Sorafenib-Induced Cardiac Dysfunction in Patients with Hepatocellular Carcinoma: Compared with F-FDG PET/CT.
Luo Y, Yang Q, Qin X … +3 more , Yu B, Jiang S, Liu Y
Mol Imaging Biol · 2025 Jun · PMID 40307657 · Publisher ↗
PURPOSE: Evaluation of F-FAPI PET/CT imaging in sorafenib-induced cardiac dysfunction in hepatocellular carcinoma (HCC) patients, and compared with F-FDG PET/CT. PROCEDURES: This retrospective study enrolled 75 HCC patie...
PURPOSE: Evaluation of F-FAPI PET/CT imaging in sorafenib-induced cardiac dysfunction in hepatocellular carcinoma (HCC) patients, and compared with F-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 F-FDG PET/CT six months after treatment, followed by F-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 F-FDG and F-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 F-FAPI high uptake, left ventricular (LV) F-FDG SUV, LV/liver F-FDG SUV, myocardial F-FAPI SUV, myocardial/aorta F-FAPI SUV, and myocardial/liver F-FAPI SUV. One year after treatment, the incidence of MACEs was slightly higher in the group with high F-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 F-FDG and F-FAPI PET/CT are helpful in evaluating sorafenib-induced cardiac dysfunction in HCC patients. The level of F-FAPI myocardial uptake has potential value in predicting post-treatment cardiotoxicity and overall survival prognosis in HCC patients.
Species-Specific Hepatic Uptake of [Cu]Cu-EOB-NOTA, A Newly Designed Hepatospecific PET Agent.
Fan J, Ramulu BJ, Mallett CL … +7 more , Kenney LE, Kauffman N, Bhattacharyya T, Sabbaghan M, Singh S, Zinn KR, Shapiro EM
Mol Imaging Biol · 2025 Jun · PMID 40304857 · Full text
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 su...
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 Cu chelation and transport by hepatic OATPs, [Cu]Cu-EOB-NOTA. PROCEDURES: EOB-NOTA was synthesized, its two enantiomers separated by chiral HPLC, and individually radiolabeled with [Cu]Cu. Cocktails of each enantiomer of [Cu]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, [Cu]Cu-EOB-NOTA hepatic influx and efflux was high, but slower compared to Gd-EOB-DTPA. Neither enantiomer of [Cu]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: [Cu]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.
Physiological Uptake of Ga-FAPI-04 in Female Reproductive System.
Mu J, Zhang Y, Xia Y … +5 more , Zhou Y, Gan R, Xiang Q, Su M, Jia Z
Mol Imaging Biol · 2025 Jun · PMID 40279067 · Publisher ↗
PURPOSE: Since the avid uptake of Ga-labeled fibroblast activation protein inhibitor (Ga-FAPI-04) observed in female reproductive organs, our objectives were to investigate the physiological uptake characteristics and pr...
PURPOSE: Since the avid uptake of Ga-labeled fibroblast activation protein inhibitor (Ga-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 Ga-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: 2.75 ± 0.84, IQR: 1.39-5.26; SUV: 2.72, IQR: 2.34-3.20; p = 0.315) than in postmenopausal patients (SUV: 2.27, IQR: 2.01-2.75; SUV: 2.38 ± 0.55, IQR: 1.35-3.60; p = 0.767), as well as uterine Ga-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: Ga-FAPI-04 SUVs in reproductive organs are higher in premenopausal patients than in postmenopausal patients. The Ga-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.
[F]NaF PET/CT Imaging of Iliac Bones to Assess Bone Turnover.
Singh SB, Gandhi OH, Shrestha BB … +9 more , Glennan P, Bahadur AR, Motamedi N, Khanal K, Wagle S, Høilund-Carlsen PF, Werner TJ, Revheim ME, Alavi A
Mol Imaging Biol · 2025 Jun · PMID 40274673 · Full text
PURPOSE: This study investigated the effects of laterality, age, gender, BMI, and physical activity level on iliac bone turnover using [F]NaF PET/CT. PROCEDURES: Fifty-nine males and 44 females from the CAMONA study were...
PURPOSE: This study investigated the effects of laterality, age, gender, BMI, and physical activity level on iliac bone turnover using [F]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. [F]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: [F]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. [F]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: [F]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. [F]NaF PET/CT may serve as a tool for assessing bone metabolism and turnover in asymptomatic individuals.
Immune Response to Bioluminescence Imaging Reporters in Murine Tumor Models.
Basnet A, Thomas DD, Landreth KM … +2 more , Damron FH, Liu TW
Mol Imaging Biol · 2025 Jun · PMID 40234300 · Full text
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....
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.
Comparison of the Correlation Between Cerebral [F]FDG Metabolism as Assessed by Two Asymmetry Indices and Clinical Neurological Score in Patients with Ischemic Cerebrovascular Disease.
Liang Y, Cui B, Ye L … +6 more , Yang B, Shan Y, Yang H, Ma L, Zhang M, Lu J
Mol Imaging Biol · 2025 Jun · PMID 40234299 · Full text
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...
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-[F]fluoro-D-glucose ([F]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 [F]FDG PET/MR scan one year later. Two voxel-wise AI methods, designated as AI and AI, 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 [F]FDG metabolism assessed by AI was larger than that obtained from AI (all p < 0.0001). The correlation coefficients between the clinical scores and the decreased metabolism in temporal and parietal lobes assessed by AI method were all higher than those from AI. In addition, the improved follow-up patients showed more pronounced metabolic improvement as assessed by AI. CONCLUSIONS: The assessment of cerebral [F]FDG metabolism in patients with unilateral internal carotid/middle cerebral artery steno-occlusion to reflect clinical neurological function using the AI method demonstrated superior performance in comparison to the AI method.
Assessment of Heat Stroke-Induced Brain Injury: A Preclinical Study with a Rat Model Using F-FDG Brain PET.
Kim D, Lee HW, Moon BS … +5 more , Park SM, Lee JE, Kim BS, Lee WJ, Yoon HJ
Mol Imaging Biol · 2025 Jun · PMID 40234298 · Publisher ↗
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 r...
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 F-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, F-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), 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 in the hypothalamus and significantly lower SUVR 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 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 F-FDG in the brains of lethally injured heat stroke rats compared to the controls as well as the survived rats. The F-FDG brain PET may have the potential to provide early indicators of catastrophic injury and reflect the early neurological pathophysiology of heat stroke.
Synthesis and Construction of I-124 Labeled Small Molecular Probe for Noninvasive PET Imaging of CAIX Expression.
Yang X, He C, Wang F … +5 more , Wen L, Huang H, Wang J, Yang Z, Zhu H
Mol Imaging Biol · 2025 Jun · PMID 40205275 · Publisher ↗
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 rete...
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 [I]I-XYIMSR- 01 in CAIX-overexpression tumor by using positron emission tomography (PET) imaging. PROCEDURES: [I]I-XYIMSR- 01 was labeled by I, 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: [I]I-XYIMSR- 01 was obtained with high specific activity, good radiochemical purity, and good stability. The uptake of of [I]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 [I]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 [I]I-XYIMSR- 01 is an ideal molecular probe for tumor hypoxia, enabling long-term dynamic monitoring and imaging of hypoxic tumors.
Imaging Cell Surface Plectin in PDAC Patients - A First-In-Human Phase 0 Study Report.
Dimastromatteo J, He J, Adams RB … +1 more , Kelly KA
Mol Imaging Biol · 2025 Jun · PMID 40140133 · Full text
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...
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 In 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.
Correction: Neoadjuvant Therapies Do Not Reduce Epidermal Growth Factor Receptor (EGFR) Expression or EGFR-Targeted Fluorescence in a Murine Model of Soft-Tissue Sarcomas.
Streeter SS, Xu X, Hebert KA … +7 more , Werth PM, Hoopes PJ, Jarvis LA, Pogue BW, Paulsen KD, Samkoe KS, Henderson ER
Mol Imaging Biol · 2025 Jun · PMID 40131668 · Publisher ↗
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Ex-vivo Imaging of Glial Energy Metabolism in the Neonatal Mouse Brain during Convulsive Seizures with Intranasal Radiotracer Administration.
Hosoi R, Tada K, Hayakawa T … +1 more , Haga Y
Mol Imaging Biol · 2025 Jun · PMID 40131667 · Full text
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-C]acetate. PROCEDURES...
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-C]acetate. PROCEDURES: [2-C]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-C]acetate when administrated intranasally and intravenously in 3-week-old mice. To confirm selective uptake by glial cells, [2-C]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-C]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-C]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-C]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.
Development of a CT-less SPECT Acquisition Protocol for Kidney Dosimetry in Lu-PSMA-617 Radioligand Therapy.
Happel C, Völler L, Bockisch B … +4 more , Groener D, Leonhäuser B, Grünwald F, Sabet A
Mol Imaging Biol · 2025 Jun · PMID 40111714 · Full text
PURPOSE: Targeted radioligand therapy of metastatic castration-resistant prostate cancer (mCRPC) with Lu-PSMA (RLT) requires sufficient dose monitoring of the kidneys. Currently, dosimetry using SPECT/CT-imaging is the m...
PURPOSE: Targeted radioligand therapy of metastatic castration-resistant prostate cancer (mCRPC) with Lu-PSMA (RLT) requires sufficient dose monitoring of the kidneys. Currently, dosimetry using SPECT/CT-imaging is the most preferred method. However, SPECT/CT is a time-consuming procedure and comprises additional radiation exposure to the patient. Moreover, not every therapeutic nuclear medicine facility has access to SPECT/CT. Therefore, the aim of this study was to develop a new procedure of kidney dosimetry without the use of SPECT/CT and evaluate this method in a large cohort of patients with mCRPC undergoing RLT. PROCEDURES: A dedicated torso phantom with kidneys filled with a solution of Lu-PSMA was used for quantitative calibration of a SPECT-camera. The calculated sensitivity was adapted according to the individual attenuation of the patient in four directions from the kidney surface to the body surface (ventral, dorsal, left and right) obtained from a previously performed CT. A total of 196 patients undergoing 926 cycles of Lu-PSMA therapy were retrospectively analyzed. Abdominal SPECT was performed 24, 48 and 72 h after administration of Lu-PSMA including scatter and dead-time correction in every patient. Kidney dose was calculated using an individual attenuation-based procedure and compared to values from international literature. RESULTS: Volumes of interest of the kidneys were drawn in the three sequential SPECT-images to calculate intra-renal effective half-life. Absolute quantification of activity in the kidneys was accomplished obtaining a patient individual sensitivity based on the individual attenuation in the patient. Kidney dose was then calculated applying a bi-exponential time activity curve in Microsoft EXCEL. Mean kidney dose per administered activity was 0.54 (± 0.26) Gy/GBq. CONCLUSIONS: With the presented procedure a reliable kidney dosimetry is possible without the use of SPECT/CT. Facilities without SPECT/CT are therefore able to perform an adequate kidney dosimetry without additional radiation exposure for the patient.
Background Tissue with Native Target Expression Can Determine Presence of Nodal Metastasis in Head and Neck Squamous Cell Carcinoma Patients Infused with Targeted Fluorescent Tracers.
Meeks N, James S, Krishnan G … +7 more , Wodeyar A, Tanaka H, Kasten BB, Lee YJ, Hom ME, Rosenthal EL, Warram JM
Mol Imaging Biol · 2025 Jun · PMID 40100567 · Full text
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 affect...
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.
Development of Anti-CEA C2 Domain-Deleted Antibody (M5A∆C2) for the PET Imaging of Colorectal Cancer.
Jitender J, Hong T, Sherman A … +5 more , Wong P, Aniogo E, Kujawski M, Shively JE, Yazaki PJ
Mol Imaging Biol · 2025 Apr · PMID 40085171 · Full text
PURPOSE: Recombinant antibody fragments represent a novel class of in vivo biological immunoPET imaging agents. This study developed a series of anti-carcinoembryonic antigen (CEA) C2 domain-deleted antibodies to evaluat...
PURPOSE: Recombinant antibody fragments represent a novel class of in vivo biological immunoPET imaging agents. This study developed a series of anti-carcinoembryonic antigen (CEA) C2 domain-deleted antibodies to evaluate their rapid, high-level tumor targeting combined with fast blood clearance for immunoPET imaging in two colorectal cancer mouse models. PROCEDURE: A series of humanized anti-CEA M5A∆C2 recombinant antibody fragments were synthesized via transient mammalian expression and purified using a two-step process. The M5A∆CH2 antibody series was characterized by HPLC-SEC, SDS-PAGE and binding affinities. The M5A∆C2-C5 antibody, which has five disulfide bridges in the modified IgG1/IgG3 hinge domain, was selected for positron emission tomography (PET) imaging. Site-specific thiol conjugation of the reduced hinge disulfides with the 1,4,7,10 tetraazacyclododecane-1,4,7-triacetic acid trisodium salt-vinyl sulfone (DO3A-VS) chelate was performed, followed by labeling with [Cu-CuCl]. The [Cu]Cu-DO3A-M5A∆C2-C5 was evaluated for CEA-positive tumor PET imaging at serial time points, pharmacokinetics and a terminal biodistribution study conducted in two CEA-positive colorectal cancer mouse models. RESULTS: The anti-CEA M5A∆C2 antibodies had high expression, were purified using a new CH3 domain affinity resin and were stable up to one year. ImmunoPET imaging and biodistribution studies were performed in athymic mice bearing human colorectal cancer LS174T tumors and immunocompetent transgenic-CEA (Tg-CEA) mice bearing MC-38 tumors transfected with the human CEA gene. The [Cu]Cu-DO3A-M5A∆C2-C5 showed rapid, high tumor localization and the expected fast blood clearance. CONCLUSIONS: A series of humanized anti-CEA M5A∆C2 antibodies were designed for immunoPET imaging of colorectal cancer, and the [Cu]Cu-DO3A-M5A∆C2-C5 showed high tumor targeting and fast blood clearance supporting its potential for clinical trials.
Potential of Radiomics, Dosiomics, and Dose Volume Histograms for Tumor Response Prediction in Hepatocellular Carcinoma following Y-SIRT.
Mansouri Z, Salimi Y, Hajianfar G … +8 more , Knappe L, Wolf NB, Xhepa G, Gleyzolle A, Ricoeur A, Garibotto V, Mainta I, Zaidi H
Mol Imaging Biol · 2025 Apr · PMID 40064820 · Full text
PURPOSE: We evaluate the role of radiomics, dosiomics, and dose-volume constraints (DVCs) in predicting the response of hepatocellular carcinoma to selective internal radiation therapy with Y with glass microspheres. MET...
PURPOSE: We evaluate the role of radiomics, dosiomics, and dose-volume constraints (DVCs) in predicting the response of hepatocellular carcinoma to selective internal radiation therapy with Y with glass microspheres. METHODS: Tc-macroagregated albumin (Tc-MAA) and Y SPECT/CT images of 17 patients were included. Tumor responses at three months were evaluated using modified response evaluation criteria in solid tumors criteria and patients were categorized as responders or non-responders. Dosimetry was conducted using the local deposition method (Dose) and biologically effective dosimetry. A total of 264 DVCs, 321 radiomic features, and 321 dosiomic features were extracted from the tumor, normal perfused liver (NPL), and whole normal liver (WNL). Five different feature selection methods in combination with eight machine learning algorithms were employed. Model performance was evaluated using area under the AUC, accuracy, sensitivity, and specificity. RESULTS: No statistically significant differences were observed between neither the dose metrics nor radiomicas or dosiomics features of responders and non-responder groups. Y-dosiomics models with any given set of inputs outperformed other models. This was also true for Y-radiomics from SPECT and SPECT-clinical features, achieving an AUC, accuracy, sensitivity, and specificity of 1. Among MAA-dosiomic and radiomic models, two models showed AUC ≥ 0.91. While the performance of MAA-dose volume histogram (DVH)-based models were less promising, the Y-DVH-based models showed strong performance (AUC ≥ 0.91) when considered independently of clinical features. CONCLUSION: This study demonstrated the potential of Tc-MAA and Y SPECT-derived radiomics, dosiomics, and dosimetry metrics in establishing predictive models for tumor response.
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