EJNMMI Research最新文献

Background: Brown adipose tissues (BAT) are highly vascularized, mitochondria-rich tissues involved in thermogenesis. Physiological [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) uptake in BAT can be influenced by several factors, including the use of medications that act on β-adrenergic receptors. Recently, increased [¹⁸F]FDG BAT uptake has been observed in elderly patients (≥ 60 years old) receiving β3-adrenergic receptor agonists. With the increasing use of β3-adrenergic receptor agonists for managing overactive bladder, there is limited understanding of their potential association with increased [¹⁸F]FDG BAT uptake. This study retrospectively investigated whether treatment with β3-adrenergic receptor agonists is associated with increased [¹⁸F]FDG BAT uptake among elderly patients. [¹⁸F]FDG positron emission tomography (PET) images were analyzed visually and through SUVmax measurements across eight predefined regions of interest (ROI): cervical, periclavicular, axillary, mediastinal, paravertebral, paraabdominal aortic, perirenal, and perisplenic regions. Patients' medication history and clinical records were reviewed to assess β3-adrenergic receptor agonist use relative to their [¹⁸F]FDG PET study.

Results: Forty-four elderly patients, each with a single [¹⁸F]FDG PET scan, were included in the analysis. Among the eight ROIs, the perirenal region showed a statistically significant increase in [¹⁸F]FDG BAT uptake in patients receiving β3-adrenergic receptor agonists compared with those not receiving, based on both visual analysis (p < 0.001) and SUVmax measurements (p = 0.030). All patients receiving β3-adrenergic receptor agonists demonstrated increased [¹⁸F]FDG BAT uptake in the paravertebral region.

Conclusion: In patients aged ≥ 60 years, β3-adrenergic receptor agonist therapy appears to be associated with increased [¹⁸F]FDG BAT uptake, particularly in the perirenal area.

Background: The study aims to maximize clinical scan efficiency for Total-body (TB) ¹⁸F-FDG PET/CT systems by optimizing scan strategies based on theoretical models and clinical experience from a single center.

Results: This prospective study include two parts. The first part involved simulation experiments using theoretical models to maximize patient throughput and/or minimizing radiotracer activity across four clinical scanning scenarios: fixed working time, predetermined radiotracer activity, integration of various injection activity regimens for a fixed number of patients, and incorporation of dynamic scans into routine static scans within a fixed working time. The optimal scan strategies for these scenarios were then proposed. The second part validated the estimated throughput results through high-throughput tests performed in the real clinical settings with an fixed working time of 8 h. Under a fixed working time of 8 h, the theoretical patient throughput for full-activity, half-activity, 1/3-activity, and 1/10-activity injection regimens was 60, 48, 43, 30 patients, respectively. The corresponding real clinical throughput achieved was 60, 49, 48, 28 patients. For a total ¹⁸F-FDG activity of 37,000 to 148,000 MBq (1 to 4 Ci), the 1/3-activity injection regimen yielded the highest patient throughput, ranging 52 to 72 patients. Strategically combining various injection activity regimens could reduce radiotracer activity consumption. Additionally, placing full-activity dynamic scans after routine static scans for full-activity, half-activity, and 1/3-activity, and before 1/10 activity, proved to ba more economical strategies.

Conclusions: Optimized scan strategies for typical clinical scenarios of TB ¹⁸F-FDG PET/CT systems were proposed, which could promote clinical scan efficiency and accommodate diverse clinical requirements. These strategies enable centers to balance throughput and activity efficiency while maintaining diagnostic quality.

Background: [¹⁷⁷Lu]Lu-DOTA-TATE is an effective treatment for metastatic neuroendocrine tumors (NETs) expressing somatostatin receptors. While the tumor uptake [¹⁷⁷Lu]Lu-DOTA-TATE of has shown potential as a predictive biomarker, patient response to the treatment varies significantly. In this study, we aim to identify a predictive blood-based transcriptomic biomarker to better understand individual responses to [¹⁷⁷Lu]Lu-DOTA-TATE therapy.

Results: Twenty-six patients were prospectively enrolled in this study. Responders were defined as patients who showed partial response or stable disease and non-responders were defined as patients who showed progressive disease according to RECIST1.1 criteria. Of the 26 patients, responders (n = 20) exhibited distinct gene expression profiles compared to non-responders (n = 6). Among the 21 differentially expressed genes identified between the groups, 13 genes were upregulated in non-responders and were associated with the innate immune system. Weighted Gene Co-expression Network Analysis identified a significant gene module linked to treatment response, with eEF1A1 emerging as a key hub gene correlated with favorable outcomes. Baseline clinical and laboratory parameters did not differ significantly according to treatment response.

Conclusions: This study identifies specific blood transcriptomic profiles associated with the innate immune response and a key hub gene linked to treatment outcomes, suggesting an immune-related component in response to [¹⁷⁷Lu]Lu-DOTA-TATE therapy. These findings may guide patient selection based on systemic immune markers and inform future therapeutic strategies.

Background: Cardiac amyloidosis requires quantitative assessment using technetium-99m pyrophosphate (^99mTc-PYP) single-photon emission computed tomography (SPECT)/computed tomography (CT) for adequate discrimination and evaluation of disease extent. This study aimed to evaluate the utility of standardized uptake value (SUV) analysis using ^99mTc-PYP SPECT/CT in pathologically-confirmed transthyretin amyloid cardiomyopathy (ATTR-CM). The study also explored the relationship between local uptake heterogeneity and indicators of cardiac impairment.

Methods: Forty patients diagnosed via heart biopsy and genetic analysis (20 ATTR-CM; 4 light-chain amyloidosis, 16 non-amyloidosis) were enrolled. The mean SUVs of the heart and aorta were measured using SPECT images. Discrimination performance was evaluated by comparing each SUV, the heart-to-aorta ratio (rSUV_H/Ao), and the heart-to-contralateral-lung ratio with pathological findings serving as the gold standard. Polar maps were analyzed to assess local SUV distribution in patients with ATTR-CM. The coefficient of variation (COV) of myocardial uptake, difference score between the septum and lateral wall (%DS), base-to-apex variability, and total cardiac SUV were calculated and compared with echocardiographic parameters.

Results: All metrics were significantly different between the ATTR-CM and non-amyloidosis groups. The rSUV_H/Ao effectively differentiated patients with ATTR-CM from those with light-chain or non-amyloidosis. Local myocardial SUV distribution correlated with impaired cardiac function. Notably, COV showed significant correlations with e' (R = 0.782) and E/e' (R =  - 0.625), linking heterogeneity to myocardial stiffness and diastolic dysfunction. Larger %DS, which predominantly reflected the ATTR-CM pattern of high septal uptake, correlated significantly with thinner walls (average wall thickness, R =  - 0.655; relative wall thickness, R =  - 0.486). As the total cardiac SUV increased, the %DS decreased (reflecting more homogeneous distribution), and global longitudinal strain worsened (R = 0.614). These observations indicated that greater impairment was associated with a higher disease burden.

Conclusions: This study demonstrated that quantitative SPECT analysis provides a valuable tool for the diagnostic evaluation and differentiation of ATTR-CM. The rSUV_H/Ao offers high discriminatory performance. Local heterogeneity and total myocardial uptake are closely related to the disease burden and extent, as reflected by structural and functional abnormalities on echocardiography. These findings suggest potential relevance to the non-invasive assessment of these aspects of the disease at a single time point.

Background: Gastrin releasing peptide receptor (GRPR)-targeting radiotracers have been studied (pre)-clinically with promising results. Patients eligible for this treatment are likely to have undergone prior treatments with other anti-cancer agents, including chemotherapy. Chemotherapies are known to alter cancer cell's gene expression and radiosensitivity, potentially impacting GRPR expression and the response to radionuclide therapy. We studied the effect of two commonly applied chemotherapies, doxorubicin (DXR) and docetaxel (DTX), on GRPR expression, GRPR radiotracer uptake, and response to external beam radiation therapy (EBRT) and targeted radionuclide treatment, in prostate cancer (PCa) and breast cancer (BC) cells. Additionally, in-vivo uptake of the GRPR-targeting radiotracer "NeoB" in PC-3 and T47D xenograft-bearing mice was assessed using SPECT/CT following chemotherapy treatment.

Results: DTX significantly decreased GRPR expression, radiotracer uptake, and radiosensitivity of PC-3 cells in-vitro. DXR pre-treated T47D cells demonstrated an increased GRPR expression and radiotracer uptake, and were less sensitive to EBRT. In-vivo, DTX pre-treatment increased [¹⁷⁷Lu]Lu-NeoB uptake in PC-3 xenografts, but this was not GRPR mediated. DXR pre-treatment did not alter [¹⁷⁷Lu]Lu-NeoB uptake in T47D xenografts, but an increase in GRPR mRNA expression was observed.

Conclusion: Our data demonstrated that chemotherapy alters mechanisms relevant for the success of GRPR-mediated radionuclide therapy in PCa and BC cells in-vitro. These finding were less prominent in-vivo and additional studies are needed to unravel this.

Background: Radiological imaging plays an indispensable role in both preclinical and clinical studies of multiple myeloma (MM). However, manual quantification in longitudinal small animal PET/CT is limited by annotator bias, signal artifacts from urinary/fecal excretion, and voxel misalignment due to non-rigid registration. To address these challenges and improve characterization of tumor biology, we developed a semi-automated PET/CT quantification pipeline targeting defined regions of interest (ROIs) within the bone marrow-rich mouse skeleton, achieving sub-organ spatial resolution, including in anatomically complex sites such as the pelvis. We applied this MM-specific preclinical pipeline to analyze tumor distribution in a longitudinal molecular PET study using an immunocompetent mouse model of skeletally disseminated MM. An Attention U-Net was trained to segment the thoracolumbar spine, pelvis and pelvic joints, sacrum, and femurs from 2D CT slices. A custom algorithm masked spillover signal from physiological excretion, and a PCA-based projection was used to map tumor distribution along the skeletal axis. Quantification metrics included mean and maximum standardized uptake values (SUV_mean, SUV_max) from PET and Hounsfield Units (HU) from CT to assess tumor burden, spatiotemporal tumor distribution, and bone involvement.

Results: Tumor burden localized preferentially to skeletal regions near joints. Using precise CT-based alignment (DICE = 0.966 ± 0.005), we detected early disease progression and aggressive phenotypes. A marked increase in tumor uptake was observed by day 18 post-implantation, with significant SUV_mean increases in the spine (p = 0.012), left/right femurs (p = 0.007/0.006), pelvis and pelvic joints (p = 0.018), and sacrum (p = 0.02). Notably, sex-based differences were identified: female mice showed greater bone loss near the hip joint at later stages, with significant HU_mean reductions at days 25 (p = 0.008) and 32 (p = 0.002).

Conclusions: This pipeline enables reproducible, anatomically precise quantification of region-specific trends in MM progression, including joint-specific lesion tropism and sex-based differences, from longitudinal PET/CT scans. By mitigating common challenges such as excretion artifacts and inconsistent mouse positioning, our approach overcomes limitations of manual analysis and enhances evaluation of tumor biology and treatment response in preclinical models of bone-involved cancers.

Background: Pick's disease (PiD) is classified as frontotemporal lobar degeneration with pathological tau aggregates. Positron emission tomography (PET) with ¹⁸F-florzolotau provides high-contrast imaging of diverse tau fibrils. While our previous work demonstrated the detectability of three repeat (3R) tau pathology by ¹⁸F-florzolotau PET in an autopsy-confirmed PiD patient, its potential for quantitative assessment of 3R tau aggregates in living individuals remains unclear. In this study, we analyzed correlations between in vivo ¹⁸F-florzolotau retentions and postmortem neuropathological data across brain regions in the same case with PiD.

Case presentation: The patient was 60 years of age at the time of death and had been diagnosed with behavioral variant frontotemporal dementia. The patient underwent ¹⁸F-florzolotau PET one year prior to death and was given the pathological diagnosis of PiD by brain autopsy. Regional tau pathology was assessed using Bodian's silver staining and immunohistochemistry with a monoclonal antibody (AT8). Histopathological assays revealed abundant intraneuronal Pick bodies along with neuropil threads in frontotemporal and other brain areas. In the cerebral cortex, AT8-positive areas exhibited a significant positive correlation with ¹⁸F-florzolotau binding in the corresponding regions (Pearson's r = 0.81, p < 0.001) estimated as standardized uptake value ratio corrected for partial volume effect. In contrast, no such associations were found in subcortical structures. Furthermore, a substantial proportion of Pick bodies displayed fluorescence co-labelled with florzolotau and AT8 antibodies.

Conclusions: Collectively, the present findings support the capability of ¹⁸F-florzolotau PET for the in vivo quantification of 3R tau fibrils.

Background: Sarcomas represent a heterogeneous group of mesenchymal tumors that, despite accounting for only 1% of cancers worldwide, rank among the top five causes of cancer-related deaths in patients under 20 years old. Surgical resection remains the primary treatment for these malignancies, as effective systemic therapies are limited, particularly for high-grade disease. However, surgical outcomes are often compromised by incomplete resection, leading to high local and distal recurrence rates. Intraoperative molecular imaging has emerged as a promising approach to improve surgical outcomes but has been hindered by the lack of tumor-specific targeting agents. Fibroblast activation protein (FAP), selectively expressed by mesenchymal tumors and absent in healthy tissues, presents a promising target for fluorescence-guided cancer resections.

Results: We demonstrate that 41% of human sarcomas express FAP, with expression correlating with higher histologic grade. The FAP-S0456 optical tracer specifically bound to FAP-expressing sarcomas with minimal binding to normal tissues, exhibiting excellent tumor-to-background ratios (3.8 ± 0.43). In vitro studies confirmed FAP-S0456's specificity for human FAP with a dissociation constant of approximately 10 nM. In murine xenograft models, the tracer accurately identified both primary tumors and pulmonary metastases of FAP-expressing sarcomas. Importantly, using needle confocal laser endomicroscopy, we demonstrated that FAP-S0456 enables real-time, single-cell visualization of metastatic tumor cells during surgery, including micrometastases not detected by conventional imaging.

Conclusions: FAP-S0456 represents a promising molecular imaging agent for the detection and surgical removal of primary and metastatic sarcomas. Its high specificity for FAP-expressing tumor cells, favorable biodistribution profile, and ability to detect microscopic disease offer potential to improve complete surgical resection. These findings support the development of FAP-targeted fluorescence-guided surgery for sarcoma patients, which may lead to improved oncologic outcomes, particularly for those with pulmonary metastases where complete surgical clearance is critical for survival.

Background: The mitochondrial membrane potential is a key biophysical parameter of mitochondrial function, which can be useful for the diagnosis and treatment monitoring of various cardiac diseases. We present a non-invasive PET/MR imaging method for 3D myocardial membrane potential mapping in humans.

Results: An in vivo PET/MR imaging study was performed in three healthy subjects (1 male and 2 females; 48 ± 29 years old) under a study protocol approved by the local Institutional Review Board (IRB). Written informed consent was obtained from all subjects before participation in the study. The [¹⁸F](4-Fluorophenyl)triphenylphosphonium ([¹⁸F]-FTPP⁺) PET tracer was administered using a bolus-plus-infusion protocol (bolus activity of 301.2 ± 7.6 MBq, infusion activity of 90.0 ± 4.9 MBq), where an infusion of 120 min was started shortly after the bolus injection (time of infusion, TOI). Dynamic cardiac PET/MR imaging was performed approximately 20 min after the TOI and continued for 100 min. The extracellular volume fraction mapping was performed via cardiac MR with a free-breathing, 3D cardiac T₁ mapping sequence before and after the contrast agent injection (gadoterate meglumine, 0.1 mmol/kg). A linear tangent space alignment (LTSA) model-based method was used to reconstruct high-frame-rate dynamic images from sparsely sampled (k,t)-space data for T₁. PET motion correction was performed using two steps of rigid image registration in a multi-resolution fashion, followed by a non-rigid image registration with B-spline transform. The tissue membrane potential was calculated using a kinetic model based on the Nernst equation with myocardial tracer concentration, tracer volume of distribution, and extracellular volume fraction measurements. Fully 3D membrane potential maps were successfully estimated from all three subjects. The estimated whole-heart membrane potentials were - 144.7 ± 3.5 mV, - 160.7 ± 5.3 mV, and - 165.8 ± 3.1 mV for each subject.

Conclusion: The proposed method allows 3D myocardial membrane potential mapping in humans in vivo.