PET Imaging Research Articles

Évaluation en TEP 18F-FDG de la réponse au traitement par CAR T-Cells et anticorps bispécifiques des lymphomes non hodgkiniens agressifs

Refractory or relapsing aggressive non-Hodgkin lymphomas have improved prognosis in the last few years thanks to innovative therapies such as CAR T-cells and bispecific antibodies. During these therapeutic strategies, tumoral response assessment with FDG PET remains of paramount importance. However, due to their mode of action, these treatments can result in delayed responses or in inflammatory events that may hamper interpretation of metabolic imaging. Lugano criteria, relying on the Deauville score, are useful, but it is crucial to be aware of the interpretation pitfalls and to consider all the clinical and biological background of the patient, ideally in a multidisciplinary approach.

Preclinical in vitro and in vivo evaluation of [11C]ORM-13070 as PET ligand for alpha-2C adrenergic receptor occupancy using PET imaging in non-human primates.

This paper describes the preclinical validation of the radioligand [11C]ORM-13070 and its tritiated analog for addressing selectivity and occupancy of the selective alpha-2C adrenergic receptor (α2CR) antagonist BAY 292 in the cynomolgus brain. BAY 292 is a novel drug candidate being developed for the treatment of obstructive sleep apnea (OSA) via binding to central α2CR. In vitro autoradiography studies with sections from non-diseased post-mortem human caudate revealed an excellent specific binding window (>80%) using [3H]ORM-13070. BAY 292 bound to the same binding site as [3H]ORM-13070 and generated a good specific binding signal, with greater selectivity for α2CR. In non-human primates in vivo, [11C]ORM-13070 demonstrated a reversible behavior, with uptake at baseline highest in striatum (putamen, caudate, ventral striatum, and pallidum) and low in the cerebellar cortex, consistent with the known distribution of the α2CR. A dose dependent increase in receptor occupancy after BAY 292 administration was observed, confirming BBB penetration and target engagement. The estimated EC50 for BAY 292 is 33.39 ± 11.91 ng/mL. This study aimed to demonstrate the suitability of [11C]ORM-13070 as a PET-radioligand for the study of α2CR in the non-human primate brain, and to pave the way for future clinical PET tracer studies with BAY 292.

Using interpretable deep learning radiomics model to diagnose and predict progression of early AD disease spectrum: a preliminary [18F]FDG PET study.

In this study, we propose an interpretable deep learning radiomics (IDLR) model based on [18F]FDG PET images to diagnose the clinical spectrum of Alzheimer's disease (AD) and predict the progression from mild cognitive impairment (MCI) to AD. This multicentre study included 1962 subjects from two ethnically diverse, independent cohorts (a Caucasian cohort from ADNI and an Asian cohort merged from two hospitals in China). The IDLR model involved feature extraction, feature selection, and classification/prediction. We evaluated the IDLR model's ability to distinguish between subjects with different cognitive statuses and MCI trajectories (sMCI and pMCI) and compared results with radiomic and deep learning (DL) models. A Cox model tested the IDLR signature's predictive capability for MCI to AD progression. Correlation analyses identified critical IDLR features and verified their clinical diagnostic value. The IDLR model achieved the best classification results for subjects with different cognitive statuses as well as in those with MCI with distinct trajectories, with an accuracy of 76.51% [72.88%, 79.60%], (95% confidence interval, CI) while those of radiomic and DL models were 69.13% [66.28%, 73.12%] and 73.89% [68.99%, 77.89%], respectively. According to the Cox model, the hazard ratio (HR) of the IDLR model was 1.465 (95% CI: 1.236-1.737, p < 0.001). Moreover, three crucial IDLR features were significantly different across cognitive stages and were significantly correlated with cognitive scale scores (p < 0.01). Preliminary results demonstrated that the IDLR model based on [18F]FDG PET images enhanced accuracy in diagnosing the clinical spectrum of AD. Question The study addresses the lack of interpretability in existing DL classification models for diagnosing the AD spectrum. Findings The proposed interpretable DL radiomics model, using radiomics-supervised DL features, enhances interpretability from traditional DL models and improves classification accuracy. Clinical relevance The IDLR model interprets DL features through radiomics supervision, potentially advancing the application of DL in clinical classification tasks.

Different PSMA Radiopharmaceuticals: A Comparative Study of [18F]F-PSMA-1007, [18F]F-JK-PSMA-7, and [99mTc]Tc-PSMA-I&amp;S in the Skeletal System

Background: Numerous PSMA-based tracers are used for diagnostic prostate cancer imaging, but comprehensive comparisons between multiple ligands are lacking. This study aimed to compare physiological skeletal uptake and tracer uptake in commonly recommended PSMA reference regions across three different PSMA ligands in prostate cancer patients. Methods: A total of 281 prostate cancer patients were included. Using PET and SPECT imaging, target volumes of interest were defined via a semiautomatic method, and standardized uptake values (SUV) were calculated for the skeletal system and reference regions (liver, spleen, parotid gland, and blood pool). Results: Significant differences in SUV uptake were observed, with [18F]F-PSMA-1007 showing higher SUV values in the skeletal system. The parotid gland displayed the highest variability in uptake, while the blood pool and liver exhibited more homogeneous uptake across patients. Conclusions: While radioligands behave similarly in bone regions, there are notable differences in SUV patterns, particularly for PSMA-1007, which showed higher bone uptake. Parotid gland uptake variability suggests a reconsideration of its suitability as a reference region, while the liver, spleen, and blood pool showed more consistent uptake. During comparison, the technetium-labeled SPECT ligand proved as similarly effective as the two PET ligands for diagnostic imaging.

Preliminary evaluation of FAPI-04-PET/CT for differentiating recurrence and post-treatment changes in high-grade gliomas

Fibroblast-activated protein (FAP) expression in glial cells is attributed to FAP-positive foci on tumor vessels and neoplastic cells. Preclinical and pilot studies have shown FAP expression in high-grade gliomas. We aimed at comparing PET imaging with FAP-inhibitor (FAPI-PET) with current standard, i.e., fluoro-ethyl tyrosine (FET) PET in post-treatment setting to differentiate recurrence and post-treatment changes. 6 patients with WHO Grade III and IV glioma who received standard treatment underwent Ga-68-FAPI-04 PET/CT (FAPI-PET/CT). Tracer uptake greater than background was considered positive. FET PET was performed and interpreted as per institutional standards, which formed the basis of treatment decision. There was concordance between FAPI expression and FET uptake in 5 patients suggestive of disease recurrence. There was no FAPI expression seen in 1 patient, in whom FET PET was suggestive of post-treatment changes. FAPI PET uptake correlated with amino acid expression to differentiate post treatment changes from recurrence in high-grade glial tumors; further validation with prospective study and histopathological confirmation is needed.

Novel [18F]FPG-interleukin-2 conjugate for monitoring immune checkpoint therapy with positron emission tomography

18F-interleukin-2 based PET imaging of activated T cells serves as a potential tool for non-invasive response prediction, treatment evaluation, and patient stratification in cancer immune checkpoint therapy. Herein, we report the radiolabelling of interleukin-2 (IL-2) with a novel arginine selective bioconjugation reagent, 4-[18F]fluorophenylglyoxal ([18F]FPG). Good non-decay corrected bioconjugation efficiencies of 29 ± 4 % (n = 5) were obtained for the [18F]FPG-IL-2. [18F]FPG-IL-2 uptake by the phytohemagglutinin-activated Jurkat cells (50.5 ± 1.2 %, n = 3) was significantly higher compared to the non-activated Jurkat cells (12.9 ± 1.1 %, n = 3). The [18F]FPG-IL-2 uptake was blocked by the pre-treatment of activated Jurkat cells with excess native IL-2 (22.3 ± 2.2 %, n = 3). Dynamic PET imaging and ex vivo biodistribution study of [18F]FPG-IL-2 in healthy and CT26 tumour bearing mice demonstrated hepatobiliary and renal clearance with minimal uptake in other organs and CT26 tumours. [18F]FPG-IL-2 PET imaging was applied to non-invasively monitor immune checkpoint therapy in CT26 tumour bearing mice, treated with IgG (control), ⍺PD-1 (monotherapy), and ⍺PD-1+⍺CTLA-4 (combination therapy). Significant uptake was observed in the spleens and tumours of the mice in the combination therapy group, which was associated with increased cytotoxic CD8+ T-cell infiltration and reduced tumour volumes. [18F]FPG-IL-2 based PET imaging has the potential to monitor immune checkpoint therapy.

FAP and PSMA Expression by Immunohistochemistry and PET Imaging in Castration-Resistant Prostate Cancer: A Translational Pilot Study.

Prostate-specific membrane antigen (PSMA) is a theranostic target for metastatic prostate cancer (PCa). However, castration-resistant PCa (CRPC) may lose PSMA expression after systemic therapy. Fibroblast activation protein (FAP), expressed by carcinoma-associated fibroblasts in various cancer types, including PCa, has the potential to be an alternative target. In this study, we evaluated FAP expression in CRPC to assess its potential, using PSMA as a comparison. Methods: FAP expression was assessed using immunohistochemistry in 116 CRPC tumors: 78 adenocarcinomas, 11 small cell carcinomas, and 27 anaplastic carcinomas. Correlation analysis between manual scoring and automated scoring was performed on 54 whole-slide sections of metastatic CRPC. Paired FAP and PSMA stains were assessed in tissue microarray cores of CRPC (n = 62), consisting of locally advanced CRPC (n = 9) and metastatic CRPC (n = 53). FAP and PSMA positivity was defined by an immunohistochemistry score of at least 10. To explore the correlation of PSMA and FAP inhibitor (FAPi) PET imaging and immunohistochemistry, a preliminary analysis of 4 patients included in a [68Ga]-FAPi-46 imaging trial (NCT04457232) was conducted. Results: Manual and automated scoring of FAP yielded results with strong correlations. Overall, FAP expression in CRPC was notably lower than PSMA expression (median immunoscores, 14 vs. 72; P < 0.001). Different histologic subtypes of CRPC demonstrated distinct levels of PSMA expression, whereas their FAP expression levels were comparable. Among the 19 PSMA-negative tumors, 11 (58%) exhibited FAP positivity. FAP expression levels in lymph node metastases were significantly lower than those in nonnodal metastases (P = 0.021). Liver metastases showed significant enrichment of tumors with strong FAP expression compared with nonliver lesions (P = 0.016). In the 4 clinical trial patients, the biopsied metastatic lesions showed lower uptake on FAPi PET than on PSMA PET (median SUVmax, 9.6 vs. 14.5), consistent with FAP expression that was lower than PSMA expression in the corresponding tumor biopsy samples (median immunoscores, 30 vs. 160). Conclusion: Because of the low FAP expression levels in CRPC, the utility of FAPi PET imaging may be limited. Although FAPi PET imaging may be further tested in PSMA-negative CRPC, such as small cell carcinoma, other molecular imaging modalities should be evaluated as alternative choices.

Comprehensive mapping of synaptic vesicle protein 2A (SV2A) in health and neurodegenerative diseases: a comparative analysis with synaptophysin and ground truth for PET-imaging interpretation.

Synaptic dysfunction and loss are central to neurodegenerative diseases and correlate with cognitive decline. Synaptic Vesicle Protein 2A (SV2A) is a promising PET-imaging target for assessing synaptic density in vivo, but comprehensive mapping in the human brain is needed to validate its biomarker potential. This study used quantitative immunohistochemistry and Western blotting to map SV2A and synaptophysin (SYP) densities across six cortical regions in healthy controls and patients with early-onset Alzheimer's disease (EOAD), late-onset Alzheimer's disease (LOAD), progressive supranuclear palsy (PSP), and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-GRN). We identified region in SV2A density among controls and observed disease- and region-specific reductions, with the most severe in FTLD-GRN (up to 59.5%) and EOAD. EOAD showed a 49% reduction in the middle frontal gyrus (MFG), while LOAD had over 30% declines in the inferior frontal gyrus (IFG) and hippocampus (CA1). In PSP, smaller but significant reductions were noted in the hippocampal formation, with the inferior temporal gyrus (ITG) relatively unaffected. A strong positive correlation between SV2A and SYP densities confirmed SV2A's reliability as a synaptic integrity marker. This study supports the use of SV2A PET imaging for early diagnosis and monitoring of neurodegenerative diseases, providing essential data for interpreting in vivo PET results. Further research should explore SV2A as a therapeutic target and validate these findings in larger, longitudinal studies.

18F]FDG and [68Ga]Ga-FAPI-04-Directed Imaging for Outcome Prediction in Patients with High-Grade Neuroendocrine Neoplasms.

We aimed to quantitatively investigate the prognostic value of PET-based biomarkers on [18F]FDG and [68Ga]Ga-fibroblast activation protein inhibitor (FAPI)-04 PET/CT in patients with highly aggressive neuroendocrine neoplasms (NENs) and to compare the visually assessed differences in uptake on both examinations with progression-free survival (PFS). Methods: In this single-center retrospective analysis, 20 patients with high-grade NENs had undergone [18F]FDG and [68Ga]Ga-FAPI-04 PET. Both PET scans were visually compared, and the presence of [18F]FDG-positive, [68Ga]Ga-FAPI-04-negative (FDG+/FAPI-) lesions was noted. In addition, we assessed maximum, peak, and mean SUV; tumor volume (TV); and total lesion uptake (TLU = TV × SUVmean) for both radiotracers using a 40% lesion-based threshold. The results of quantitative and visual analysis were correlated with PFS using log-rank analysis or univariate Cox regression. PFS was defined radiographically using RECIST 1.1., clinically using signs of disease progression, or as death. Results: Most primary tumors were located in the gastrointestinal tract (13/20 patients, 65%) or were cancer of unknown primary (5/20 patients, 25%). FDG+/FAPI- lesions were found in 9 of 20 patients (45%). Patients with FDG+/FAPI- lesions had a significantly decreased PFS of 4 mo, compared with 9 mo for patients without FDG+/FAPI- metastases (P = 0.0063 [log-rank test]; hazard ratio [HR], 5.637; 95% CI 1.619-26.16; P = 0.0110 [univariate Cox regression]). On univariate analysis, a significant correlation was also found between PFS and TV for both radiotracers ([18F]FDG: mean TV, 258 ± 588 cm3; HR, 1.024 [per 10 cm3]; 95% CI, 1.007-1.046; P = 0.0204) ([68Ga]Ga-FAPI-04: mean TV, 130 ± 192 cm3; HR, 1.032 [per 10 cm3]; 95% CI, 1.001-1.062; P = 0.0277) and TLU on [18F]FDG PET (mean TLU, 1,931 ± 4,248 cm3; HR, 1.004 [per 10 cm3]; 95% CI, 1.001-1.007; P = 0.0135). Conclusion: The presence of discordant FDG+/FAPI- lesions is associated with a significantly shorter PFS, which might indicate more aggressive disease prone to early progression. Dual-tracer PET/CT of patients with highly aggressive NENs could help guide treatment decisions or identify high-risk lesions for additional local therapeutic approaches.

Feasibility, Tolerability, and Preliminary Clinical Response of Fractionated Radiopharmaceutical Therapy with 213Bi-FAPI-46: Pilot Experience in Patients with End-Stage, Progressive Metastatic Tumors.

Radiopharmaceutical therapies (RPTs) based on fibroblast activation protein (FAP) and FAP inhibitors (FAPIs) are a new option for progressive metastatic cancer in patients pretreated multiple times. To date, published in-human data refer to initial experiences with β-emitting 90Y- and 177Lu-based RPT. However, the short tumor retention time of FAPI ligands is considered a major limitation of FAPI RPT. Therefore, fractionated FAPI RPT with 213Bi, an α-emitter with a half-life of 46 min, appears to be a promising FAPI RPT regimen. Here, we report on our initial experiences with regard to the feasibility, tolerability, and response of fractionated 213Bi-FAPI-46 RPT. Methods: Six patients (4 women and 2 men) with progressive metastatic solid tumors (3 colon cancer, 1 anal cancer, 1 breast cancer, and 1 prostate cancer) aged 16-77 y were treated with a mean of 1,609 MBq of 213Bi-FAPI-46, fractionated into 53 single applications (range, 5-12 RPT applications per patient; mean, 8.8 applications) over a period of up to 107 h per patient. Of the 6 patients, 4 patients received adjuvant treatment with pembrolizumab. 18F-FDG (4 patients) and 68Ga-FAPI-46 (5 patients) PET/CT scans were performed before and after RPT. PET images were assessed visually and by calculating total lesion glycolysis and total lesion FAPI. Results: RPT with 213Bi-FAPI-46 was well tolerated without adverse side effects. In terms of visual response assessment, there was 1 partial response (16.7%), 1 patient with stable disease (16.7%), and 4 patients with progressive disease (66.7%). Concordantly, total lesion glycolysis and total lesion FAPI were decreased in the responding patient (not applicable and -24.3%, respectively), slightly decreased in the patient with stable disease (-10.6% and -5.9%, respectively), and increased in the 4 patients with progression (mean, +104.4% and +321.3%, respectively). Conclusion: Fractionated FAPI RPT with the short-half-life α-emitter 213Bi-FAPI-46 is a promising approach that matches the pharmacokinetics of FAPI-46 better than the 177Lu- or 90Y-labeled compounds. In this pilot project, fractionated RPT with 213Bi-FAPI-46 showed good clinical tolerability and even led to regressive or stable disease in the short term in 2 of 6 patients. Further studies with larger patient cohorts are required to evaluate the actual efficacy and long-term effects of this variant of FAPI RPT.

Individual-level metabolic connectivity from dynamic [18F]FDG PET reveals glioma-induced impairments in brain architecture and offers novel insights beyond the SUVR clinical standard.

This study evaluates the potential of within-individual Metabolic Connectivity (wi-MC), from dynamic [18F]FDG PET data, based on the Euclidean Similarity method. This approach leverages the biological information of the tracer's full temporal dynamics, enabling the direct extraction of individual metabolic connectomes. Specifically, the proposed framework, applied to glioma pathology, seeks to assess sensitivity to metabolic dysfunctions in the whole brain, while simultaneously providing further insights into the pathophysiological mechanisms regulating glioma progression. We designed an index (Distance from Healthy Group, DfHG) based on the alteration of wi-MC in each patient (n = 44) compared to a healthy reference (from 57 healthy controls), to individually quantify metabolic connectivity abnormalities, resulting in an Impairment Map highlighting significantly compromised areas. We then assessed whether our measure of metabolic network alteration is associated with well-established markers of disease severity (tumor grade and volume, with and without edema). Subsequently, we investigated disruptions in wi-MC homotopic connectivity, assessing both affected and seemingly healthy tissue to deepen the pathology's impact on neural communication. Finally, we compared network impairments with local metabolic alterations determined from SUVR, a validated diagnostic tool in clinical practice. Our framework revealed how gliomas cause extensive alterations in the topography of brain networks, even in structurally unaffected regions outside the lesion area, with a significant reduction in connectivity between contralateral homologous regions. High-grade gliomas have a stronger impact on brain networks, and edema plays a mediating role in global metabolic alterations. As compared to the conventional SUVR-based analysis, our approach offers a more holistic view of the disease burden in individual patients, providing interesting additional insights into glioma-related alterations. Considering our results, individual PET connectivity estimates could hold significant clinical value, potentially allowing the identification of new prognostic factors and personalized treatment in gliomas or other focal pathologies.

Recent Updates of PET in Lymphoma: FDG and Beyond

Lymphoma is one of the most common cancers worldwide, categorized into Hodgkin lymphoma and non-Hodgkin lymphoma. 18F-fluorodeoxyglucose positron emission tomography (FDG PET) has become an essential imaging tool for evaluating patients with lymphoma in terms of initial diagnosis, staging, prognosis, and treatment response assessment. Recent advancements in imaging technology and methodologies, along with the development of artificial intelligence, have revolutionized the evaluation of complex imaging data, enhancing the diagnostic and predictive power of PET in lymphoma. However, FDG is not cancer-specific, but it primarily reflects glucose metabolism, which has prompted the investigation of alternative PET tracers to address this limitation. Novel PET radiotracers, such as fibroblast activation protein inhibitors targeting the tumor microenvironment, have recently shown promising results in evaluating various malignancies compared to FDG PET. Furthermore, with the rapid advancements in immunotherapy and the favorable imaging properties of 89Zr, immunoPET has emerged as a promising modality, offering insights into the functional and molecular status of the immune system. ImmunoPET can also facilitate the development of new antibody therapeutics and radioimmunotherapy by providing pharmacokinetic and pharmacodynamic data. This review provides comprehensive insights into the current clinical applications of FDG PET in lymphoma, while also exploring novel PET imaging radiotracers beyond FDG, discussing their mechanisms of action and potential impact on patient management.

Predictive value of metabolic parameters and apparent diffusion coefficient derived from 18F-FDG PET/MR in patients with non-small cell lung cancer

BackgroundMultiple models intravoxel incoherent motion (IVIM) based 18F-fluorodeoxyglucose positron emission tomography-magnetic resonance(18F-FDG PET/MR) could reflect the microscopic information of the tumor from multiple perspectives. However, its value in the prognostic assessment of non-small cell lung cancer (NSCLC) still needs to be further explored.ObjectiveTo compare the value of 18F-FDG PET/MR metabolic parameters and diffusion parameters in the prognostic assessment of patients with NSCLC.Meterial and methodsChest PET and IVIM scans were performed on 61 NSCLC patients using PET/MR. The maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), diffusion coefficient (D), perfusion fraction (f), pseudo diffusion coefficient (D*) and apparent diffusion coefficient (ADC) were calculated. The impact of SUVmax, MTV, TLG, D, f, D*and ADC on survival was measured in terms of the hazard ratio (HR) effect size. Overall survival time (OS) and progression-free survival time (PFS) were evaluated with the Kaplan–Meier and Cox proportional hazard models. Log-rank test was used to analyze the differences in parameters between groups.Results61 NSCLC patients had an overall median OS of 18 months (14.75, 22.85) and a median PFS of 17 months (12.00, 21.75). Univariate analysis showed that pathological subtype, TNM stage, surgery, SUVmax, MTV, TLG, D, D* and ADC were both influential factors for OS and PFS in NSCLC patients. Multifactorial analysis showed that MTV, D* and ADC were independent predicting factors for OS and PFS in NSCLC patients.ConclusionMTV, D* and ADC are independent predicting factors affecting OS and PFS in NSCLC patients. 18F-FDG PET/MR-derived metabolic parameters and diffusion parameters have clinical value for prognostic assessment of NSCLC patients.

Tracer-Separator: A Deep Learning Model for Brain PET Dual-Tracer (18F-FDG and Amyloid) Separation.

Multiplexed PET imaging revolutionized clinical decision-making by simultaneously capturing various radiotracer data in a single scan, enhancing diagnostic accuracy and patient comfort. Through a transformer-based deep learning, this study underscores the potential of advanced imaging techniques to streamline diagnosis and improve patient outcomes. The research cohort consisted of 120 patients spanning from cognitively unimpaired individuals to those with mild cognitive impairment, dementia, and other mental disorders. Patients underwent various imaging assessments, including 3D T1-weighted MRI, amyloid PET scans using either 18F-florbetapir (FBP) or 18F-flutemetamol (FMM), and 18F-FDG PET. Summed images of FMM/FBP and FDG were used as proxy for simultaneous scanning of 2 different tracers. A SwinUNETR model, a convolution-free transformer architecture, was trained for image translation. The model was trained using mean square error loss function and 5-fold cross-validation. Visual evaluation involved assessing image similarity and amyloid status, comparing synthesized images with actual ones. Statistical analysis was conducted to determine the significance of differences. Visual inspection of synthesized images revealed remarkable similarity to reference images across various clinical statuses. The mean centiloid bias for dementia, mild cognitive impairment, and healthy control subjects and for FBP tracers is 15.70 ± 29.78, 0.35 ± 33.68, and 6.52 ± 25.19, respectively, whereas for FMM, it is -6.85 ± 25.02, 4.23 ± 23.78, and 5.71 ± 21.72, respectively. Clinical evaluation by 2 readers further confirmed the model's efficiency, with 97 FBP/FMM and 63 FDG synthesized images (from 120 subjects) found similar to ground truth diagnoses (rank 3), whereas 3 FBP/FMM and 15 FDG synthesized images were considered nonsimilar (rank 1). Promising sensitivity, specificity, and accuracy were achieved in amyloid status assessment based on synthesized images, with an average sensitivity of 95 ± 2.5, specificity of 72.5 ± 12.5, and accuracy of 87.5 ± 2.5. Error distribution analyses provided valuable insights into error levels across brain regions, with most falling between -0.1 and +0.2 SUV ratio. Correlation analyses demonstrated strong associations between actual and synthesized images, particularly for FMM images (FBP: Y = 0.72X + 20.95, R2 = 0.54; FMM: Y = 0.65X + 22.77, R2 = 0.77). This study demonstrated the potential of a novel convolution-free transformer architecture, SwinUNETR, for synthesizing realistic FDG and FBP/FMM images from summation scans mimicking simultaneous dual-tracer imaging.

68Ga]Ga-FAPI04 Outperforms [18F]FDG PET/CT for Detecting Nodal Metastasis of Head and Neck Squamous Cell Carcinoma: A Single-Center Experience.

This study assesses fibroblast activated protein inhibitor (FAPI) targeted PET/CT imaging against [18F]FDG PET/CT (FDG PET) for detecting nodal involvement in head and neck squamous cell carcinoma (HNSCC), intending to improve diagnostic precision for metastatic lymph nodes and lay the groundwork for future investigations. Methods: Patients diagnosed with HNSCC were retrospectively enrolled. All patients underwent [68Ga]Ga-FAPI04 PET/CT (FAPI PET) and FDG PET within 6 d. Primary tumor, lymph nodes, and tracer uptake were visually and quantitatively compared. The metastatic lymph nodes were evaluated using patient-and lesion-based analyses, with biopsy or postoperative histopathological examination as the reference. Results: The cohort includes 24 patients (17 men, 7 women; mean age 60 ± 11.8 years) who underwent FDG and FAPI PET for preoperative diagnostic workup or restaging due to known recurrence of HNSCC. Lesions included 24 primary tumors, 54 cervical lymph nodes, and 5 metastases. Primary tumors exhibited significant uptake on both PET modalities (median maximum standardized uptake value [SUVmax]: FDG 19.4 ± 11.6, FAPI 16.9 ± 4.6), with no statistically significant difference (p > 0.5). For lymph nodes, FAPI and FDG PET showed median SUVmax of 9.18 ± 6.77 and 9.67 ± 6.5, respectively. The patient-based analysis found FDG PET sensitivity at 88.2% and FAPI PET at 94.1%, with FAPI PET specificity significantly higher (85.7% vs. 42.8% for FDG PET). Lesion-based analysis revealed FAPI PET sensitivity and specificity at 84.2% and 93.7%, respectively, contrasting FDG PET's at 81.5% and 25%, respectively. Conclusion: This study underscores the efficacy of FAPI PET in detecting primary tumors in HNSCC. Furthermore, FAPI PET shows improved specificity over FDG PET for metastatic lymph nodes advocating further investigations for integrating FAPI PET into HNSCC clinical protocols for its enhanced precision in detecting metastatic lymph nodes.

PET imaging of pheochromocytoma and paraganglioma - 18F-FDOPA vs. somatostatin analogues.

Functional imaging with positron emission tomography (PET) scans is an essential part of the diagnostic workup for pheochromocytoma and paraganglioma (PPGL). The purpose of this review is a) to provide a brief overview of functional imaging for PPGL, b) summarize selected present and older guideline and review recommendations, and c) conduct a literature review on the diagnostic performance of the most used PET tracers for PPGL. We conducted a systematic literature search in PubMed from January 2004 to August 2024 with the search string: ("Pheochromocytoma" OR "Paraganglioma") AND ("Positron-Emission Tomography" OR "Radionuclide Imaging" OR ("PET" AND ("FDG" OR "DOTATOC" OR "DOTANOC" OR "DOTATATE" OR "DOPA" OR "FDOPA"))). Studies involving PET scans of at least 20 individuals with PPGL, or at least five individuals in a rare, well-defined subgroup of PPGL (e.g. sympathetic or head-neck paragangliomas, and specific pathogenic variants) were included. Seventy studies were identified of which 21 were head-to-head comparisons of at least two different PET tracers (18F-fluorodihydroxyphenylalanine, 18F-FDOPA; 68Ga-DOTA-conjugated somatostatin analogues, 68Ga-SSA; and 18F-fluorodeoxyglucose, 18F-FDG). 18F-FDOPA had higher sensitivity for pheochromocytoma compared to 68Ga-SSA and equal sensitivity for metastatic pheochromocytoma. 18F-FDOPA and 68Ga-SSA had similar sensitivity for primary non-SDHx sympathetic and head-neck paraganglioma. However, 68Ga-SSA had higher sensitivity for metastatic sympathetic and head-neck paraganglioma and for SDHx-related paraganglioma. 18F-FDOPA and 68Ga-SSA PET are both sensitive for localizing PPGL. However, 18F-FDOPA is the most sensitive for detecting pheochromocytoma, while 68Ga-SSA is superior to 18F-FDOPA for metastatic sympathetic and head-neck paraganglioma and SDHx-related paraganglioma.

Evaluation of Targeted Alpha Therapy Using [211At]FAPI1 in Triple-Negative Breast Cancer Xenograft Models.

Triple-negative breast cancer (TNBC) presents limited therapeutic options and is associated with poor prognosis. Early detection and the development of novel therapeutic agents are therefore imperative. Fibroblast activation protein (FAP) is a membrane protein expressed on cancer-associated fibroblasts (CAFs) that plays an essential role in TNBC proliferation, migration, and invasion. Consequently, it is hypothesized that the Astatine (211At)-labeled FAP inhibitor (FAPI) selectively exerts anti-tumor effects through alpha-particle emission. In this study, we aimed to assess its theranostic capabilities by integrating [18F]FAPI-74 PET imaging with targeted alpha therapy using [211At]FAPI1 in TNBC models. Mice xenografts were established by transplanting MDA-MB-231 and HT1080 cells (control). As a parallel diagnostic method, [18F]FAPI-74 was administered for PET imaging to validate FAP expression. A single dose of [211At]FAPI1 (1.04 ± 0.10 MBq) was administered to evaluate the therapeutic efficacy. [18F]FAPI-74 exhibited high accumulation in MDA-MB-231 xenografts, and FAP expression was pathologically confirmed via immunostaining. The group that received [211At]FAPI1 (n = 11) demonstrated a significantly enhanced anti-tumor effect compared with the control group (n = 7) (p = 0.002). In conclusion, [18F]FAPI-74 PET imaging was successfully used to diagnose FAP expression, and as [211At]FAPI1 showed promising therapeutic efficacy in TNBC models, it is expected to be a viable therapeutic option.

Evaluation of 18F FOL a PET tracer targeting folate receptor beta in a rat model of myocardial infarction

Abstract Background Expression of folate receptor-β (FR-β) on the activated macrophages is associated with inflammatory diseases. However, the role of FR-β in the immune response following myocardial infarction (MI) remains unknown. Purpose To investigate FR-β-targeted positron emission tomography (PET) tracer aluminium fluoride-18-labeled 1,4,7,-triazacylononane-1,4,7-triacetic acid conjugated folate ([18F]FOL) for imaging immune response in a rat model of MI. Methods Rats underwent PET scan from 20 to 40 minutes after injection of 50±6 MBq of [18F]FOL on 3 (n=6), 7 (n=21), 15 (n=9), and 90 (n=11) days after surgical ligation of the left coronary artery. As controls, rats were studied on 3 (n=6), 7 (n=14), 15 (n=5), and 90 (n=8) days after sham-operation. [18F]FDG PET was performed a day before [18F]FOL injection in order to localize myocardium and area of MI. After [18F]FOL PET, autoradiography, histology, and staining of CD68 were performed 3 (n=6), 7 (n=6), and 90 (n=11) days after MI in order to detect [18F]FOL uptake and activated macrophages in myocardial tissue sections. A subgroup of rats (n=15) underwent serial [18F]FOL PET 7 and 90 days after MI together with echocardiography in order to evaluate left ventricular function. Results The presence of MI was confirmed by histology in all rats after coronary ligation. PET images showed increased uptake of [18F]FOL in the area of MI. The uptake was significantly higher (p&amp;lt;0.001) in the area of MI than in the myocardium of sham-operated rats on day 3 (SUV 2.04±0.25 vs. 0.74±0.12), and remained increased on day 7 (SUV 1.39±0.33 vs. 0.68±0.12), day 15 (SUV 1.24±0.20 vs. 0.59±0.07), and day 90 (SUV 1.39±0.25 vs. 0.69±0.11). On day 3, pre-treatment with folate glucosamine (n=3) reduced the [18F]FOL signal by 50% in the area of MI indicating specific binding to FR-β. Autoradiography confirmed focally increased uptake of [18F]FOL in the area of MI. A positive correlation was found between uptake of [18F]FOL in PET images and areal percentage of CD68-positivity in the area of MI (r2=0.447, p&amp;lt;0.001). Uptake of [18F]FOL on day 7 after MI was associated with decline in left ventricular ejection fraction (R=-0.665, p&amp;lt;0.01) and increase in left ventricular systolic volume (R=0.561, p=0.02) between 7 and 90 days after MI. Conclusion Cardiac [18F]FOL PET detects increased macrophage-associated FR-β expression after MI in a rat model. FR-β expression peaks early and remains elevated up to 3 months in the infarcted area. Increased FR-β expression early after MI is associated with worsening of left ventricular systolic function late after MI.

The role of 18fluorine-fluorodeoxyglucose positron emission tomography in the diagnosis, follow-up, and regulation of treatment in patients with cardiac sarcoidosis.

Abstract Background Cardiac sarcoidosis (CS) is a potentially fatal disease, commonly presenting with arrhythmias, heart failure, or sudden death. Diagnostic challenges persist, particularly due to limited sensitivity of endomyocardial biopsy (20-25%). Alternative diagnostic approaches, such as criteria-based diagnosis, have emerged. 18fluorine-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) has gained prominence in diagnosing CS, monitoring treatment, and serving as a follow-up tool, although its precise role and efficacy remain unclear. Purpose This retrospective cohort study sought to characterize patients with CS who underwent at least one 118F-FDG-PET scan. Primary objectives were to explore the impact of 18F-FDG-PET on both the diagnosis and management of CS. Additionally, this study aimed to investigate any differences in patient outcomes based on the results of their first follow-up 18F-FDG-PET scan. Methods Medical records of 69 patients with CS who underwent at least one 18F-FDG-PET scan were analyzed. The study calculated the proportion of 18F-FDG PET scans influencing CS treatment and diagnosis, with 56 patients undergoing at least two scans. Among these, 53 patients were categorized into two groups based on their first follow-up scan results (group 1:no change/progress, group 2:regress). Statistical analyses included independent t-tests, the Mann-Whitney test, and Fisher's exact test. Outcome measures included death, heart transplantation or aborted cardiac death, with survival analyzed by Kaplan-Meier statistics. Results Among 69 patients, 204 18F-FDG-PET scans were conducted, with 47% directly influencing treatment decisions. Twenty-five patients were diagnosed with CS through 18F-FDG-PET. While no significant differences were observed regarding demographics and clinical features, the results suggested potential differences in event-free survival (p=0.084;Figure 1) and sex (p=0.08) between the groups. Conclusions 18F-FDG-PET has emerged as a pivotal tool in regulating treatment, diagnosing, and monitoring CS patients, playing a fundamental role in assessing treatment response. However, further studies are needed.

A randomized, double-blind, placebo-controlled, mechanistic trial on the safety, tolerability and pharmacodynamics of ninerafaxstat in patients with angina and chronic coronary syndrome

Abstract Background/Introduction Symptoms of angina resulting from reversible myocardial ischemia in chronic coronary syndromes have a negative impact on quality of life. Metabolic alterations are a key feature of ischemia, including reduced ATP generation by mitochondrial oxidative phosphorylation, NAD+ depletion, anaerobic glycolysis, proton &amp; lactate accumulation leading to contractile dysfunction. Ninerafaxstat is a novel cardiac mitotrope that shifts metabolism from fatty acids towards glucose utilization, optimizing myocardial energy production during ischemia. Purpose We aimed to investigate the safety, tolerability, impact on myocardial glucose utilization and preliminary anti-ischemic efficacy of ninerafaxstat administered for 8 weeks to patients with symptomatic chronic stable angina who were on anti-anginal therapy and had evidence of myocardial stress hypoperfusion using 15O-H2O PET imaging. Methods IMPROVE-Ischemia was an international, randomized, double-blind, placebo-controlled mechanistic trial comparing ninerafaxstat vs. placebo in patients with symptomatic chronic coronary syndrome. The primary endpoint was the safety and tolerability of ninerafaxstat. Key efficacy evaluations were undertaken at baseline and end-of-treatment (Week 8) including imaging core laboratory assessments of 15O-H2O PET perfusion rest and stress imaging to quantify absolute myocardial blood flow (MBF), dobutamine stress echo with contrast for evaluation of LV contractile response during demand stress using the wall motion score index (WMSI) and, in a subgroup of subjects, 18F-FDG-PET imaging of myocardial glucose metabolism. Results The study randomized 58 subjects (mean age 68.6±7.1 years) with symptomatic stable angina and inducible hypoperfusion from 4 sites across 3 countries (Denmark, Finland, Sweden). 22% had type 2 diabetes and 50% had undergone percutaneous and/or surgical coronary revascularization. The majority (68%) were on ≥2 (up to 4) regular anti-anginals. Ninerafaxstat was well tolerated without impact on systemic hemodynamics. At Week 8, ninerafaxstat significantly increased myocardial glucose utilization and, in those with dobutamine-induced deterioration in wall motion at baseline assessment (n=25, pre-specified subgroup), resulted in a ~50% improvement in mean and peak stress WMSI, without altering rest or hyperemic stress MBF (Table 1). Conclusion(s) Treatment with ninerafaxstat was well-tolerated and showed a neutral hemodynamic profile. Ninerafaxstat significantly increased myocardial glucose utilization consistent with its mechanism of action and improved myocardial contractile response to dobutamine stress in subjects with baseline stress inducible deterioration of wall motion. These findings support a direct, metabolically-mediated, anti-ischemic effect of ninerafaxstat on top of existing anti-anginal agents, supporting its further development in cardiac pathologies characterised by ischemia.