Annals of Nuclear Medicine最新文献

Objective

Amyloid-β (Aβ) aggregates have been recognized as therapeutic targets for Alzheimer’s disease (AD). Targeted alpha therapy (TAT) using α-particles has the potential to be applied as a novel treatment approach for AD by reducing the quantity of Aβ aggregates. In this study, we developed a novel astatine-211-labeled pyridyl benzofuran (PBF) derivative, [²¹¹At]APBF-2, as a small molecule-based Aβ-TAT agent and evaluated its potential for in vivo use.

Methods

[²¹¹At]APBF-2 was synthesized in a one-step astatination process using the tributyltin precursor. In the Aβ aggregation inhibition assay, [²¹¹At]APBF-2 was added to a sample containing Aβ_1–42 monomers and thioflavin-T (ThT) and the mixture was incubated for 24 h. The quantity of Aβ aggregates was evaluated by measuring ThT fluorescence intensity. The biodistribution of [²¹¹At]APBF-2 (25 kBq/100 μL) was evaluated using ddY mice (n = 5).

Results

[²¹¹At]APBF-2 was synthesized in radiochemical yield of 57% with a radiochemical purity of over 95%. In the in vitro assay, [²¹¹At]APBF-2 showed a dose-dependent decrease in ThT fluorescence intensity, suggesting the ability of [²¹¹At]APBF-2 to inhibit Aβ aggregation. In the biodistribution study using normal mice, the initial brain uptake of [²¹¹At]APBF-2 was observed (2.95% injected dose/g at 2 min), demonstrating favorable Blood–brain barrier permeability.

Conclusions

These results suggest the feasibility of using [²¹¹At]APBF-2 as an Aβ-TAT agent for in vivo applications.

Objective

Tumor-infiltrating lymphocytes (TILs) are key immune biomarkers associated with prognosis and treatment response in early-stage breast cancer (BC), particularly in the triple-negative subtype. This study aimed to evaluate whether [18F]FDG PET/CT imaging and routine cell blood count (CBC)-derived biomarkers can serve as non-invasive surrogates for TILs, using machine-learning models.

Material and methods

We retrospectively analyzed 358 patients with biopsy-proven early-stage invasive BC who underwent pre-treatment [18F]FDG PET/CT imaging. PET-derived biomarkers were extracted from the primary tumor, lymph nodes, and lymphoid organs (spleen and bone marrow). CBC-derived biomarkers included neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). TILs were assessed histologically and categorized as low (0–10%), intermediate (11–59%), or high (≥ 60%). Correlations were assessed using Spearman’s rank coefficient, and classification and regression models were built using several machine-learning algorithms.

Results

Tumor SUVmax and tumor SUVmean showed the highest correlation with TIL levels (ρ = 0.29 and 0.30 respectively, p < 0.001 for both), but overall associations between TILs and PET or CBC-derived biomarkers were weak. No CBC-derived biomarker showed significant correlation or discriminative performance. Machine-learning models failed to predict TIL levels with satisfactory accuracy (maximum balanced accuracy = 0.66). Lymphoid organ metrics (SLR, BLR) and CBC-derived parameters did not significantly enhance predictive value.

Discussion

In this study, neither [18F]FDG PET/CT nor routine CBC-derived biomarkers reliably predict TILs levels in early-stage BC. This observation was made in presence of potential scanner-related variability and for a restricted set of usual PET metrics. Future models should incorporate more targeted imaging approaches, such as immunoPET, to non-invasively assess immune infiltration with higher specificity and improve personalized treatment strategies.

Objective

To analyze the imaging characteristics of FDG PET/CT in pericardial effusions from various etiologies and evaluate its diagnostic utility for differentiating these etiologies.

Methods

A retrospective analysis was conducted on 71 patients who underwent FDG PET/CT imaging for etiological diagnosis of pericardial effusion from 2014 to 2024 in our hospital. Clinical, laboratory, and imaging data from FDG PET/CT were evaluated to characterize pericardial effusions attributable to malignant conditions, bacterial infections, other benign etiologies, and idiopathic causes, thus assessing the diagnostic efficacy of FDG PET/CT.

Results

Pericardial lesions exhibited significant thickening and markedly increased FDG uptake in 89.5% of malignant cases and 77.8% of bacterial infection cases. When integrated with extrapericardial imaging findings, FDG PET/CT directly identified the underlying etiology in 68.4% of malignant and 44.4% of bacterial infection cases. Employing an integrated "clinical-laboratory-imaging" diagnostic approach, the positive diagnostic rate of FDG PET/CT increased to 56.3%, and FDG PET/CT was able to achieve etiologically suggestive imaging diagnoses in 100% of malignant cases, 77.8% of bacterial cases, and 47.8% overall. Ultimately, FDG PET/CT contributed to clinical management in 88.7% of patients.

Conclusion

FDG PET/CT is valuable for the etiological diagnosis of pericardial effusions. Developing a comprehensive "clinical-laboratory-imaging" diagnostic model can substantially enhance the effectiveness of FDG PET/CT in determining the underlying causes of pericardial effusion.

Theranostics, a novel integrated approach that combines cancer diagnosis and therapy by switching the radionuclide, has attracted growing attention. Various oncology PET probes other than FDG have been developed for the highly sensitive and precise detection of many types of cancer with the advancements in PET scanners, supporting the innovative development in theranostics. In therapeutic applications, radioligand therapy targeting somatostatin receptors (SSTR) and prostate-specific membrane antigen (PSMA) has already demonstrated significant clinical benefits. Terbium-161 (¹⁶¹Tb) has emerged as a new beta and Auger electron emitter, showing greater therapeutic efficacy compared to ¹⁷⁷Lu. Alpha emitters, such as astatine (²¹¹At), are currently being evaluated in investigator-initiated clinical trials, with preliminary efficacy data reported for [²¹¹At]NaAt in patients with radioiodine-refractory thyroid cancer. Novel pan-tumor targeting agents, such as TROP-2, Nectin-4, LAT1, GPC-1, and EphA2, are also under development, and clinical translation of radioligand therapy is anticipated. These innovations in theranostics are expected to further broaden the scope of precision medicine in oncology.

¹⁸F-Fluciclovine was the first ¹⁸F-labeled amino acid PET tracer to be approved for clinical use in Japan, receiving regulatory approval in March 2021 and being listed for reimbursement in June 2024. In response to this development, the Japanese Society of Nuclear Medicine initiated the formulation of clinical guidelines to ensure the appropriate use of this radiopharmaceutical in clinical practice. This guideline provides a comprehensive overview of the clinical characteristics of ¹⁸F-Fluciclovine in malignant glioma, including indications for use, imaging protocols, interpretation of PET images, and considerations for radiation safety. The Japanese version of this guideline was compiled by a voluntary editorial committee and officially approved by the Japanese Society of Nuclear Medicine on August 16, 2024. The primary objective of this guideline is to consolidate the current scientific evidence on ¹⁸F-Fluciclovine and to clarify its clinical utility, appropriate usage, and imaging methodologies. By doing so, it aims to promote the proper implementation of ¹⁸F-Fluciclovine in clinical settings and to serve as a reference for future applications related to the expansion of insurance coverage and reimbursement decisions.

It is recommended that PET examinations using ¹⁸F-Fluciclovine in Japan be conducted in accordance with this guideline. Although the content is tailored to the Japanese medical system and regulatory framework, the imaging protocols, radiation safety management, and interpretation methods described herein are also expected to be internationally applicable and relevant.

Objective

To investigate the prognostic value of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) in patients with mucosal melanoma of the head and neck (MMHN) treated with carbon ion radiotherapy (CIRT).

Methods

This single-center retrospective study included patients with MMHN who underwent CIRT and FDG-PET/CT. Correlations between pre-treatment FDG-PET/CT-derived parameters, including the maximum standardized uptake variable (SUVmax), metabolic tumor volume (MTV) with a 50% threshold, total lesion glycolysis (TLG), bone marrow/liver SUVmax and mean standardized uptake variable (SUVmean) ratios, and spleen/liver SUVmax and SUVmean ratios (SLRmax, SLRmean), with clinical parameters and prognosis were statistically analyzed.

Results

A total of 32 patients with MMHN were enrolled (median age, 72.5 years). The tumor stages were distributed as follows: T3, 17 patients; T4a, 14 patients; T4b, one patient. The median total observation period was 22.6 months, the median overall survival (OS) was 21.6 months, and the median progression-free survival (PFS) was 11.5 months. Thirteen patients (40.6%) died, 10 (31.3%) experienced local recurrence, and 19 (59.4%) had distant metastases during the observation period. The 1 and 3-year survival rates were 78.1% and 62.5%, respectively. FDG-PET/CT showed pronounced positive uptake for all tumors (median SUVmax: 13.8, range 2.7–33.0). SLRmax was high in patients with negative programmed death-ligand 1 expression in the tumor (p = 0.05). PFS was shorter in patients with a high MTV (p = 0.018). In the multivariate analysis, MTV was an independent prognostic factor for PFS (hazard ratio, 2.60; 95% confidence interval, 1.065–6.345; p = 0.036). MTV and TLG were not predictive of OS in the univariate analysis.

Conclusions

FDG-PET/CT showed a strong positive uptake for MMHN. FDG-PET/CT-derived imaging parameters may be significant prognostic biomarkers for predicting tumor progression in patients with MMHN.

Purpose

Brown adipose tissue (BAT) contributes to thermoregulation and energy expenditure. Although BAT is abundant in early childhood and declines with age, its distribution across age groups remains unclear. This study examined age-related BAT distribution using fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT).

Materials and methods

A total of 8695 FDG-PET/CT scans performed for clinical purposes were retrospectively reviewed. FDG accumulation with a standardized uptake value (SUV) max > 1.5 in known BAT regions was considered positive. BAT distribution patterns were classified into T-type (positive accumulation in the supraclavicular or axillary region), I-type (positive accumulation in the cervical or paravertebral region without supraclavicular or axillary involvement), lipomatous hypertrophy of the interatrial septum (LHIS)-type (positive accumulation localized only to the LHIS), and others (cases not fitting any type).

Results

BAT accumulation was observed in 78 patients (0.9% prevalence): T-type (18), I-type (39), LHIS-type (18), and others (3). The mean ages for T-type, I-type, LHIS-type, and others were 29.8 ± 17.3, 73.6 ± 18.1, 72.9 ± 12.5, and 67.0 ± 11.5 years, respectively. Patients in the T-type group were significantly younger than those in the I-type- and LHIS-type groups (p < 0.01).

Conclusions

This study identified three BAT distribution types, with T-type occurring in mostly younger compared with the I-type and LHIS type. Recognizing these patterns may improve FDG-PET/CT diagnostic accuracy.

Recent advances in PET image reconstruction have focused on achieving high image quality and quantitative accuracy. Bayesian penalized likelihood (BPL) algorithms, such as Q.Clear and HYPER Iterative that have been integrated into commercial PET systems offer robust image noise suppression and edge preservation through regularization. In parallel, methods based on deep learning such as SubtlePET, AiCE, uAI^® HYPER DLR, and Precision DL have emerged primarily as post-processing techniques. They use trained convolutional neural networks to reduce image noise while preserving lesion contrast. These methods have reduced image acquisition times or reduced radiotracer doses while maintaining diagnostic confidence. uAI^® HYPER DPR represents a hybrid approach by embedding deep learning in iterative reconstruction. This review summarizes the technical principles and the clinical performance of BPL and deep learning-based PET reconstruction algorithms, and discusses key considerations such as image quality and quantitative accuracy of PET images. This review should deepen understanding of advanced PET image reconstruction techniques and accelerate their clinical implementation across diverse PET imaging applications.

Objective

Vision language models (VLMs) allow visual input to Large Language Models. VLMs have been developing rapidly, and their accuracy is improving rapidly. Their performance in nuclear medicine compared to state-of-the-art models, including reasoning models, is not yet clear. We evaluated state-of-the-art VLMs using problems from the past Japan Nuclear Medicine Board Examination (JNMBE) and assessed their strengths and limitations.

Methods

We collected 180 multiple-choice questions from JNMBE (2022–2024). About one-third included diagnostic images. We used eight latest VLMs. ChatGPT o1 pro, ChatGPT o1, ChatGPT o3-mini, ChatGPT-4.5, Claude 3.7, Gemini 2.0 Flash thinking, Llama 3.2, and Gemma 3 were tested. Each model answered every question three times in a deterministic setting, and the final answer was set by majority vote. Two board-certified nuclear medicine physicians independently provided reference answers, with a third expert resolving disagreements. We calculated overall accuracy with 95% confidence intervals and performed subgroup analyses by question type, content, and exam year.

Results

Overall accuracies ranged from 36.1% (Gemma 3) to 83.3% (ChatGPT o1 pro). ChatGPT o1 pro achieved the highest score (150/180, 83.3% [95% CI: 77.1–88.5%]), followed by ChatGPT o3-mini (82.8%) and ChatGPTo1 (78.9%). All models performed better on text-only questions than on image-based ones; ChatGPT o1 pro correctly answered 89.5% of text questions versus 66.0% of image questions. VLMs demonstrated limitations in handling with questions on Japanese regulations. ChatGPT 4.5 excelled in neurology-related image-based questions (76.9%). Accuracy was slightly lower from 2022 to 2024 for most models.

Conclusions

VLMs demonstrated high accuracy on the JNMBE, especially on text-based questions, but exhibited limitations with image recognition questions. These findings show that VLMs can be a good assistant for text-based questions in medical domains but have limitations when it comes to comprehensive questions that include images. Currently, VLMs cannot replace comprehensive training and expert interpretation. Because VLMs evolve rapidly and exam difficulty varies annually, these findings should be interpreted in that context.

Background and objective

In neuroinflammation, activated astrocytes, called reactive astrocytes, highly express monoamine oxidase B (MAO-B). [¹⁸F]SMBT-1 is a novel PET tracer developed for imaging neuroinflammation, with highly selective binding to MAO-B. The quantification method for [¹⁸F]SMBT-1 PET imaging has not been established, although some human studies using [¹⁸F]SMBT-1 PET imaging have already been conducted. In this study, we explored the most appropriate method for quantifying [¹⁸F]SMBT-1 PET.

Methods

Dynamic PET scanning of [¹⁸F]SMBT-1, accompanied by serial arterial blood sampling, was performed in healthy elderly subjects. With PET and blood data, the total distribution volumes (Vts) in the brain regions were calculated using a one-tissue compartment model (1TCM), a two-tissue compartment model (2TCM), and Logan graphical analysis. Standardized uptake values (SUVs) and SUV ratio-1 (SUVR-1) were determined for different time frames and reference regions.

Results

The values of the χ² criterion and Akaike's Information Criterion (AIC) in the brain regions were lower in 2TCM than in 1TCM, suggesting that 2TCM was a better model in terms of curve fitting. However, the very high coefficient of variation (%COV) for parameters such as K1, k2, k3, and k4 in 2TCM suggests that these parameters may not have been properly estimated. SUVs, especially at 50–70 and 70–90 min post-injection, were strongly correlated with Vt (r = 0.9188–0.9445, p < 0.0001). SUVR-1 at these time points, referenced to various regions, showed significant correlations with MAO-B distribution in the brain shown in a previous postmortem study (r = 0.9362–0.9399, p < 0.0001).

Conclusions

These findings suggest that SUVR-1, especially at 50–70 min and 70–90 min post-injection, reflects MAO-B distribution and is useful for quantifying [¹⁸F]SMBT-1 PET imaging, potentially enabling noninvasive assessment of neuroinflammation in the brain.

Trial registration

Japan Registry of Clinical Trials (jRCT) (jRCTs021200019). It was registered on August 25, 2020. The jRCT was approved as a member of the Primary Registry Network of the WHO ICTRP.