Here, we present a precision oncologic approach for localized prostate cancer (PCa) in a 66-year-old man. Overcoming the limitations of conventional MRI in delineating tumor extent and multifocality, preoperative 68 Ga-PSMA PET/MRI precisely defined the index lesion and excluded metastases. This diagnostic workflow was directly translated into therapy through PET/MRI-US fusion-guided irreversible electroporation (IRE). The procedure targeted the tumor accurately while sparing surrounding functional anatomy. Significant PSA and phi decline post-IRE confirmed therapeutic efficacy. This case demonstrates that integrating molecularly targeted diagnostics with advanced image-guided focal therapy enables maximal precision in oncologic control.

Amyloid-β PET (Aβ-PET) imaging is playing an increasingly important role in the diagnosis and treatment of Alzheimer’s Disease (AD). The Centiloid (CL) scale has been developed to standardize the measurements of Aβ PET imaging. Previous CL threshold settings were based on PET/CT, while our team’s preliminary study found that CL values from PET/MRI are higher than those from PET/CT. Therefore, there is an urgent need to establish clinical interpretation cutoffs for Aβ status via PET/MRI to facilitate application in clinical practice. The clinical performance of Aβ PET/MRI and cerebrospinal fluid biomarkers were evaluated in a multisite cohort of 720 participants. Aβ-PET scans were visually read and quantified using CL method. A two-cutoff approach identified thresholds maintaining > 90

The 18 F-FDG and 68 Ga-FAPI-04 PET/CT imaging findings were reported in a 52-year-old man with hepatocellular carcinoma (HCC) 3 weeks after undergoing yttrium-90 selective internal radiation therapy ( 90 Y-SIRT). Both viable tumors and tumor thrombus of right portal vein showed mild-to-moderate 18 F-FDG uptake, while peritumoral tissues showed high 68 Ga-FAPI-04 uptake, the range of which approximately matched radiotracer distribution on 90 Y SPECT/CT. Our findings indicate that 18 F-FDG PET/CT is superior to 68 Ga-FAPI-04 PET/CT for identifying viable HCC tumors during early 90 Y-SIRT monitoring, whereas 68 Ga-FAPI-04 PET/CT indirectly delineates the area of 90 Y-SIRT.

In total-body positron emission tomography and computed tomography (PET/CT) imaging, reducing the radiation dose of diagnostic CT scans is essential for minimizing overall radiation exposure, particularly in pediatric patients. Although deep learning-based denoising methods have shown promise in restoring low-dose CT (LDCT) to normal-dose CT (NDCT) quality, most approaches rely on structurally aligned paired data, which are difficult to acquire in clinical practice. Models trained on synthetic pairs often exhibit limited generalizability to real LDCT data. Unconditional diffusion models demonstrate outstanding generalizability, but fail to preserve structural fidelity. To address these challenges, we propose an enhanced diffusion posterior sampling (E-DPS) framework that combines a one-step denoiser U-Net with an unconditional diffusion model. Specifically, the U-Net estimator, trained on simulated LDCT-NDCT pairs, provides preliminary denoised outputs as structural constraints, whereas the diffusion model captures the prior distribution of NDCT images to enhance realism and generalizability. During inference, the U-Net predictions are integrated as constraints with tunable weights, thereby guiding diffusion posterior sampling. In addition, an intermediate-stage initialization strategy is introduced, significantly reducing the number of required sampling steps. Extensive experiments on simulated LDCT datasets across three dose levels demonstrate the superiority of our method, yielding average PSNR gains of +5.2% and +4.3% at unseen dose levels compared with state-of-the-art approaches. Moreover, on real LDCT images, E-DPS exhibits strong zero-shot generalizability, achieving better noise suppression while preserving anatomical detail. These results highlight the robustness and clinical potential of E-DPS for LDCT denoising.

Low-count positron emission tomography (PET) reduces injected activity or acquisition time, but fewer detected coincidence events compromise image quality and quantitative reliability. Existing diffusion-based PET enhancement methods commonly use generic, count-agnostic Gaussian schedules that do not explicitly represent acquisition/count-dependent variation in degradation severity between paired standard- and low-count reconstructions. Direct incorporation of multi-step history may also complicate Markovian reverse inference. We propose a count-informed, endpoint-conditioned diffusion bridge in the reconstructed-image domain with gated autoregressive inference (GAI). The bridge is anchored to paired reconstructed endpoints: its conditional mean follows the standard-to-low-count residual, while a normalized expected-count trajectory controls progression along that residual and the aggregate latent variance. Measurement-level Poisson counting statistics motivate this trajectory from acquisition duration or injected-activity ratio, but no Poisson likelihood is imposed on reconstructed PET voxels. During reverse inference, GAI summarizes previous reverse states within an augmented state that retains a first-order Markov formulation and permits closed-form, count-conditioned updates. We evaluated the method on four-center total-body [18F]FDG short-duration PET datasets and a simulated BrainWeb low-dose dataset. On the Shanghai Ruijin cohort, it increased PSNR by 5.33 dB and SSIM by 0.043 and reduced RMSE by 53.4% for 3s acquisitions relative to the unenhanced short-duration PET (sdPET) input. At 1s, PSNR increased by 5.91 dB and RMSE decreased by more than 60%. BrainWeb provided proof-of-concept evidence under controlled count reduction. These results support count-informed degradation modeling for low-count PET enhancement in the reconstructed-image domain.

The overexpression of somatostatin receptor (SSTR) in neuroendocrine neoplasms (NENs) provides a molecular basis for treatment with peptide receptor radionuclide therapy (PRRT). However, heterogeneous SSTR expression limits therapeutic efficacy. Immune checkpoint inhibitors (ICIs) enhance the abscopal effect of external radiotherapy. This study investigated whether combining PRRT using the SSTR antagonist [177Lu]Lu-DOTA-JR11 with anti-PD-L1 monoclonal antibody (mAb) therapy could enhance the abscopal effect in an SSTR2-heterogeneous bilateral tumor model. A bilateral SSTR2-heterogeneous murine melanoma model was established by contralateral implantation of B16F10-SSTR2 and B16F10-wildtype tumors. Mice received saline, PRRT, anti-PD-L1 mAb, or combination therapy. Tumor growth, survival, PET/CT imaging, histopathology, immune profiling (including PD-L1 expression, CD45+ cells, CD8+ cells, myeloid-derived suppressor cells [MDSCs], and macrophage phenotypes), and serum cytokine levels were assessed to evaluate local and systemic antitumor responses. PRRT monotherapy selectively inhibited SSTR2-positive tumors but showed minimal efficacy against SSTR2-negative tumors. Combination therapy significantly suppressed the growth of both tumors, prolonged survival, and reduced [18F]FDG uptake in tumors. These effects were accompanied by increased Granzyme B expression, enhanced CD8+ cell infiltration, expansion of M1 macrophages and effector memory T cells, and reductions in MDSCs and M2 macrophages. Serum IFN-γ and IL-2 levels were significantly elevated, indicating robust systemic immune activation. PRRT combined with PD-L1 blockade remodels the tumor immune microenvironment, elicits potent systemic antitumor immunity, and enhances the abscopal effect in SSTR2-heterogeneous tumors. This strategy may help address target-expression heterogeneity in radionuclide therapy.

PURPOSE:This study aimed to report rapid off-line total-body positron emission tomography/computed tomography (PET/CT) imaging in pediatric patients after proton craniospinal irradiation (CSI), which enabled visualization of the entire craniospinal axis together with whole-body redistribution of proton-induced activity. METHODS AND MATERIALS:Three pediatric patients with medulloblastoma or pineoblastoma underwent 60-minute dynamic, single-bed total-body PET/CT scans shortly after proton CSI using a rapid near-room transfer workflow. PET data were reconstructed into consecutive 5-minute frames and cumulative acquisitions to characterize regional temporal changes and acquisition duration-dependent image variability. RESULTS:PET visualized activity along the full CSI axis and in extra-field major blood vessels and blood-rich organs. Regional PET signal decreased by 92.0%-94.8% in the cranial and spinal regions and by 89.4%-91.9% in the cardiac blood pool, liver, and spleen from the 0-5-minute to the 55-60-minute frame, reflecting the combined effects of physical decay and biological washout. The first 5 minutes of PET data depicted the major whole-body distribution pattern, whereas acquisitions of ∼20- 30 minutes substantially reduced regional image variability. CONCLUSIONS:Rapid total-body PET/CT enabled single-bed visualization of the full craniospinal irradiation axis and quantitative characterization of whole-body temporal evolution after proton CSI.

Prostate cancer (PCa), a most prevalent urologic malignancy in men, remains a therapeutic challenge due to limited targeted strategies. This study investigates heat shock protein 60 (HSP60) (HSPD1-encoded), employing multi-dimensional approaches to decipher its oncogenic role and develop siRNA-loaded extracellular vesicles (siRNA@EVs) for PCa targeted therapy. Bioinformatics screening identified HSPD1 overexpression in PCa, which was validated via qPCR/Western blot in clinical tissues and cell lines. Metabolomic-transcriptomic integration and molecular biology experiments revealed HSP60-mediated glycolytic reprogramming. EVs were harvested from UV-irradiated PCa cells via high-speed centrifugation. siRNA@EVs were constructed via electroporation and evaluated in vitro (glycolysis phenotyping: glucose consumption, lactate/pyruvate production, hexokinase activity, and ATP production) and in vivo using xenograft models. Data were analyzed using R 4.3.1 and GraphPad Prism 9.0 (two-tailed t-test, P < 0.05). Multiple bioinformatics analyses (DepMap/TCGA/HPA) confirmed that HSP60 is specifically overexpressed and associated with advanced PCa progression and poor prognosis. HSPD1 knockdown and pharmacological HSP60 inhibition suppressed proliferation, metastasis, and subcutaneous tumor growth, while overexpression exacerbated oncogenicity. Multi-omics integration revealed HSP60 enhances glycolysis via p53 suppression, driving metabolic reprogramming. siRNA@EVs achieved significant HSPD1 silencing, effectively inhibiting the proliferation and metastasis of PCa cells, and blocking xenografts tumor growth in nude mice with safety. siRNA@EVs targeting HSPD1 demonstrate precision therapeutic potential with robust efficacy and safety, offering a novel approach for targeted therapy in PCa.

We presented the imaging findings of 18 F-FDG and 68 Ga-HER2 affibody PET/CT in a 52-year-old woman with HER2-positive accessory breast cancer in the right axilla. 18 F-FDG and HER2 PET/CT showed avid uptake of multiple axillary lesions. HER2 PET/CT identified extensive bone metastases with intense uptake, while the ⁹⁹ᵐTc-MDP whole bone scan was negative, and only a few bone lesions with mild tracer uptake were detected by 18 F-FDG PET/CT. Following 6 cycles of the TCbHP regimen, the axillary lesions markedly reduced. This case demonstrates that HER2 PET/CT enables more sensitive detection of HER2-positive lesions, thereby allowing for precise staging and guiding HER2-targeted therapy.

PURPOSE:To evaluate whether mucosal boron heterogeneity measured using fluoro-boronophenylalanine positron emission tomography (18F-BPA PET) improves the prediction of oral mucositis in boron neutron capture therapy (BNCT), and to establish an imaging-guided framework for normal tissue complication probability (NTCP) modeling. METHODS AND MATERIALS:This retrospective study analyzed 45 BNCT treatment sessions for head and neck cancer. Pre-treatment 18F-BPA PET was used to quantify PET-derived mucosal uptake and to derive an uptake-defined mucosal region using a tissue-to-blood ratio (TBR) threshold of 1.8. Four mucosal dose-calculation workflows were compared: (1) the Finnish workflow and (2) the Japanese workflow-both delineating mucosa anatomically and assuming uniform boron concentration implemented via a fixed TBR; (3) anatomical mucosa and (4) uptake-defined mucosa with heterogeneous boron distribution derived from PET-derived uptake heterogeneity. Biological (Gy-equivalent) and physical (Gy) subvolume dose metrics, including dose to the hottest 0.05 cubic centimeters (D0.05cc), were evaluated for correlation with mucositis severity, discrimination of grade ≥ 2 toxicity, and suitability for NTCP modeling. RESULTS:18F-BPA PET demonstrated pronounced functional heterogeneity across the mucosa. Among all evaluated metrics, uptake-defined biological D0.05cc showed the strongest and most consistent association with toxicity, fulfilling all NTCP validity criteria yielding the highest discriminative performance (repeated cross-validated area under the curve, 0.738 ± 0.025) and physiologically plausible TD10-TD90 thresholds (4.85-12.84 Gy-equivalent). In contrast, Finnish and Japanese anatomical maximum-dose metrics, based on uniform-boron assumptions, showed no meaningful correlation with clinical outcomes. CONCLUSIONS:Functional PET imaging reveals clinically important mucosal heterogeneity that influences BNCT toxicity. The uptake-defined biological D0.05cc demonstrated superior prediction of oral mucositis and may provide a promising hypothesis-generating framework for developing patient-specific mucosal dose constraints, pending prospective validation.

Rationale: Sigma-1 receptor (sigma-1R) is a promising biomarker and therapeutic target for ischemic stroke. However, the real-time changes in the expression of sigma-1R post-stroke have not been elucidated. (R)-1-(4-[18F]Fluorobenzyl)-4-[(tetrahydrofuran-2-yl)methyl]piperazine ((R)-[18F]FBFP) has emerged as a novel radiotracer targeting sigma-1R. This study aimed to use (R)-[18F]FBFP PET imaging for the investigation of spatiotemporal alterations in sigma-1R expression in the rat brain following stroke and treatment, and to explore the correlation between the imaging findings and neurological outcomes. Methods: Sigma-1R levels were evaluated on days 1, 3, 7, 14, 21, and 28 after middle cerebral artery occlusion (MCAO) using (R)-[18F]FBFP PET/CT imaging. Ex vivo autoradiography and immunofluorescence (IF) staining were performed to corroborate the findings from PET/CT imaging. The cellular localization of sigma-1R during stroke progression was identified by co-labeling sigma-1R with neurons (NeuN), astrocytes (GFAP), and microglia (Iba1). Behavioral tests were conducted on MCAO rats at corresponding time points, and the correlation between PET signals and neurological outcomes was analyzed. The MCAO rats were then treated with recombinant tissue-type plasminogen activator (rtPA), and the therapeutic response was evaluated with (R)-[18F]FBFP to elucidate the impact of treatment on PET imaging. Results: Compared with the sham group, the ipsilateral-to-contralateral hemisphere uptake ratio of (R)-[18F]FBFP of the MCAO group significantly decreased in the acute phase (days 1 and 3), increased in the subacute phase (days 7 and 14), and then gradually declined in the chronic phase (days 21 and 28). The PET imaging findings were in agreement with the ex vivo autoradiography and IF staining. Changes in sigma-1R levels in ischemic lesions were influenced by the initial neuronal loss and the later accumulation of glial cells. Furthermore, there was a significant correlation between the uptake of (R)-[18F]FBFP and the neurological outcomes during stroke recovery. After rtPA treatment, the (R)-[18F]FBFP uptake in the affected hemisphere gradually returned to levels comparable to the contralateral hemisphere. Conclusions: (R)-[18F]FBFP PET imaging effectively visualized and accurately quantified the spatiotemporal alterations of sigma-1R in the rat brain during ischemic stroke progression. The (R)-[18F]FBFP uptake correlated with the neurological outcomes during stroke recovery, and (R)-[18F]FBFP PET imaging could be a valuable tool for predicting post-stroke recovery and evaluating the efficacy of rtPA treatment.

PURPOSE:To evaluate the radioactive distribution patterns of [ 68 Ga]Ga-FAPI-04 in primary hepatocellular carcinoma (HCC). METHODS:Twenty-three primary HCC patients (26 lesions) from a prospective trial (ChiCTR2000039099) underwent both [ 18 F]FDG and [ 68 Ga]Ga-FAPI-04 PET/CT within 1 week. Uptake at tumor margins versus centers was compared. RESULTS:FAPI-04 uptake was significantly higher at tumor margins than centers (SUVmax, P <0.001; SUVmean, P <0.01). As SUVmax thresholds increased, FAPI volume of interest concentrated at the margins and decreased sharply in the centers. CONCLUSIONS:[ 68 Ga]Ga-FAPI-04 PET/CT demonstrated higher marginal uptake and pronounced central heterogeneity (low-SUV centers) in HCC. Strong peripheral uptake supports the use of FAP-targeted fluorescence-guided surgery and targeted treatment of marginal residual/recurrent disease, while low central uptake may limit FAP-targeted therapy.

Most studies on fibroblast activated protein (FAP)-targeted radiopharmaceuticals focus on administered radioactivity, often overlooking the impact of a molar dose on tumor-targeting and off-target accumulation. Here, we investigate the effect of molar dose on biodistribution and pharmacokinetics using [68Ga]Ga-FAPI-04 PET and systematically evaluated two FAP-targeted dimers, DOTAGA.(SA.FAPi)2 and DOTAGA.Glu.(FAPi)2, in a 4T1 syngeneic tumor model. Dynamic PET imaging confirmed a clear molar dose-dependent effect on tumor uptake, tumor-to-organ ratios, and organ pharmacokinetics with lower molar doses prolonging tumor retention. Comparative analyses across multiple molar doses revealed that DOTAGA.Glu.(FAPi)2 achieved comparable tumor uptake to DOTAGA.(SA.FAPi)2 but exhibited significantly reduced liver accumulation. An optimal molar dose range of 8-32 nmol/kg was identified, balancing maximal tumor uptake with reduced off-target exposure. At this optimized dose, [177Lu]Lu-DOTAGA.Glu.(FAPi)2 demonstrated therapeutic efficacy in 4T1 tumor-bearing mice with limited systemic toxicity. These results establish molar dose optimization as a broadly applicable strategy for accurately evaluating and comparing FAP-targeted radiopharmaceuticals and provide a methodological framework to guide future preclinical development and translational studies.

Percutaneous ethanol injection (PEI) is a first-line ablation therapy for hepatocellular carcinoma (HCC), while effective postoperative management remains challenging. Type I collagen in HCC stroma, linked to resistance and recurrence, is a promising target for imaging-guided theranostic. We developed a dual-modality tracer, [⁶⁸Ga]Ga/[¹⁷⁷Lu]Lu-DOTA-COL, designed to integrate noninvasive PET imaging with local radiotherapy by selectively targeting exposed type I collagen post-PEI. [⁶⁸Ga]Ga-DOTA-COL exhibited high radiochemical purity (> 99

The rapid advancements in PET technology, coupled with the need for accurate and efficient imaging, necessitate the development of robust and generalizable methods for CT-free attenuation and scatter correction (ASC). Deep learning offers a promising solution, but exhibits limited performance when tested in diverse clinical settings and varying imaging conditions. We propose a few-shot fine-tuning paradigm that enables efficient adaptation of models from a source domain to a new target domain. Our backbone network incorporates statistical modulation to extract domain-specific distribution information and employs pixel-wise factor scaling modeling to disentangle ASC factor maps from input images. On a large and diverse dataset of 1539 subjects across multiple tracers, scanners, and centers, we evaluate model performance under single-tracer training, multi-tracer joint training, and few-shot adaptation strategies. Although joint training demonstrates strong performance on known tracers, the proposed few-shot adaptation approach, CrossPET-Adapt, excels at adapting to unseen domains with minimal data, outperforming joint training. This method significantly reduces radiation exposure and data requirements, offering a rapid and robust solution for CT-free PET ASC in varied clinical environments.

Off-line PET imaging after proton therapy is limited by transport delay and by the sensitivity and short axial field of view of conventional scanners, which hinder imaging at ultralow activity and characterization of whole-body biologic washout. We evaluated whether a near-room total-body PET/CT system could enable clinically practical imaging of proton-induced activity after treatment and its whole-body biologic washout. Methods: We conducted a series of phantom studies to evaluate the performance of total-body PET at ultralow activity with Monte Carlo (MC)-simulated activity distributions as references. Nineteen patients with solid tumors underwent off-line total-body dynamic PET/CT imaging shortly after proton therapy. Spatial correlation between PET and MC results was quantified using the Dice similarity coefficient (DSC) and normalized cross-correlation (NCC). Dynamic images were reconstructed, and time-activity curves were extracted from volumes of interest to analyze the dynamic behavior of proton-induced activity. Results: In phantom experiments, PET images showed close spatial correspondence to MC reference distributions under ultralow activity. In patients, the agreement between PET and MC was higher for relatively stationary targets, with a mean DSC/NCC of 0.81 ± 0.09/0.81 ± 0.09 for the brain and 0.81 ± 0.05/0.83 ± 0.08 for the breast. Dynamic total-body PET images revealed biologic washout and whole-body redistribution of isotope activity within and beyond the gross tumor volumes, showing enrichment within the cardiac blood pool, major blood vessels, and blood-rich organs, such as the spleen and liver. Conclusion: Near-room total-body PET/CT enabled interpretable imaging under ultralow activity after treatment. Dynamic total-body imaging additionally captured whole-body biologic washout of proton-induced activity through blood circulation, providing a foundation for future washout modeling and methodologic development for in vivo treatment assessment.

Thyroid metastasis from clear cell renal cell carcinoma (ccRCC) is uncommon. The imaging findings were reported in a 77-year-old ccRCC woman with thyroid metastasis using carbonic anhydrase IX (CAIX)-targeted PET/CT. Intense radiotracer uptake was observed not only in the primary renal tumor, but also in a focal lesion in the left thyroid lobe. This case highlights the potential utility of CAIX-targeted PET/CT imaging for visualizing primary and metastatic ccRCC, including uncommon metastatic sites.

Abstract Epidural fibrosis (EF) is a frequent and debilitating complication that impairs recovery following spinal surgery, yet effective targeted therapies are lacking. Here we observe enrichment of FAP⁺ fibroblasts at surgical sites in patients after laminectomy. To therapeutically target this subset, we develop bispecific antibody–decorated extracellular vesicles (BsAb EVs), which redirect endogenous T cells to eliminate FAP⁺ fibroblasts in situ. In a preclinical model, BsAb EVs selectively eliminate pathogenic fibroblasts, reduce fibrotic collagen accumulation, and prevent the development of postoperative epidural fibrosis without detectable systemic toxicity under the tested conditions. Single-cell RNA sequencing reveals that FAP⁺ fibroblasts represent a transcriptionally distinct subset from α-SMA⁺ myofibroblasts, characterized by enhanced extracellular matrix remodeling and TGF-β production. Together, these findings highlight a critical stromal subset in EF pathogenesis and position BsAb EVs as a promising immunotherapeutic strategy for targeting pathogenic stromal cells in fibrotic and tissue-remodeling disorders.

Positron emission tomography (PET) imaging endows the possibility of precise diagnosis and effective treatment of diseases. Aromatic (hetero)cycle is one of the most fundamental groups in pharmaceuticals as well as in the development of PET tracers. In particular, incorporation of 18F to aromatic (hetero)cycles has accelerated the progress of nuclear medicine tracers. Current trend indicates a rapid progress in 18F-labeling of aromatic (hetero)cycles for PET imaging. Transition metal-catalyzed 18F-labeling method speeds up the reaction by lowering the activation energy of the substrate by the metal complex. The reaction conditions are mild, and a wide range of substrates can be used. In this article we systematically reviewed the methods of radioactive 18F-labeling of aromatic (hetero)cycles with different precursors mediated by transition metals‑copper, ruthenium, nickel, palladium, silver, and titanium. The precursors, radiolabeling conditions, catalytic efficiency, catalytic mechanism, optimization of transition metal-catalyzed 18F-labeling methods, and corresponding frontier applications of 18F-labeled molecular probes were discussed.