EJNMMI Research最新文献

Background: Spatial filters are required to suppress the statistical noise of SPECT images but with an unavoidable smoothing effect that further decreases the SUV and contrast. This study assesses a deep-learning noise reduction (DLNR) algorithm, previously developed to further reduce bone SPECT recording time on a high-speed whole-body 360° CZT-camera, when used instead of, rather than in addition to, the conventional spatial filters (CSF) recommended for this camera.

Results: The SUVmax of bone lesions (114 definite arthritis or metastasis lesions) and the resolution recovery coefficients of small and medium phantom spheres, were higher for DLNR than CSF or the combination of CSF plus DLNR (CSF-DLNR) (all p < 0.001), whereas the relative noises were lower for DLNR or CSF-DLNR, as compared with CSF (p < 0.001). Consequently, contrast-to-noise ratio (CNR) was dramatically higher for DLNR, as compared with CSF, and also CSF-DLNR, especially for small- and medium-sized structures. Compared with CSF, DLNR provided an almost two-fold CNR increase for the sphere and lesions in the range of one cm³. This dramatic CNR improvement was still documented when DLNR was compared with the median, kernel, Butterworth, or Gaussian filters used alone and set to provide an equivalent image noise reduction to DLNR on the phantom.

Conclusion: When used alone, this DLNR algorithm enhances the contrast-to-noise ratio and quantification of bone lesions, especially those of small or medium sizes. It outperforms conventional spatial filters and provides remarkable image quality for routine analysis of bone SPECT from the high-speed whole-body 360° CZT camera. However, further research and validation studies are still necessary before a widespread adoption in clinical practice.

Key points: Question: How does a deep-learning noise reduction algorithm, previously developed to further reduce bone SPECT recording times on a high-speed whole-body 360° CZT-camera, work when used instead of, rather than in addition to, the conventional spatial filters recommended for this camera. Pertinent findings: When used alone, this deep-learning noise reduction algorithm provides a high level of image denoising and better preserves the activities of small- to medium-sized bone structures and lesions than conventional spatial filters do, leading to a dramatic increase in the corresponding contrast-to-noise ratios.

Implications for patient care: Such a deep-learning noise reduction algorithm could be used not only to reduce SPECT recording time when added to conventional spatial filters, but also to improve image quality and resolution when used alone.

Trial registration: clinicaltrials.gov, NCT06782438, Registered 27 February 2025,https://clinicaltrials.gov/search?id=NCT06782438.

Background: Epithelial ovarian cancer (EOC) has the highest mortality rate among gynecological malignancies, primarily due to frequent late-stage diagnosis and the development of resistance to chemotherapy. The aim of this study was to evaluate the expression of tumor-associated targets in a large cohort (n = 179) of various EOC subtypes, represented on two tissue microarrays (TMAs), to support the future development of radionuclide therapies. The study primarily assessed folate receptor-alpha and -beta isoforms (FRα and FRβ), but also somatostatin receptor-2 (SSTR2), prostate-specific membrane antigen (PSMA) and fibroblast activation protein (FAP), for which established radiopharmaceuticals already exist. Membranous expression of these targets on tumor cells was detected by immunohistochemistry using antibodies validated on xenografts with known target expression and semi-quantitatively evaluated.

Results: Validation of the employed antibodies confirmed specific staining of the respective targets. The TMAs included tumors of high-grade and low-grade serous, endometrioid, clear cell, mucinous and carcinosarcoma. High FRα expression was seen in several EOC histotypes, most frequently in high-grade serous (47%), while it was largely absent in mucinous EOC. The FRβ was expressed only in stromal cells. SSTR2 and PSMA were only present in 8% and 4% of the EOC cases and not associated to a specific subtype. FAP expression on tumor cells was found in 10% of all EOCs, while stromal FAP was seen in 47% of the cases, with the highest prevalence in high-grade serous EOC (42%).

Conclusions: The findings of this study indicate that approved radionuclide therapies targeting SSTR2 or PSMA are unlikely to be suitable for treating EOC. In contrast, the frequent and high expression of FRα in tumor cells and FAP in tumor-associated stromal cells suggests that FRα- and FAP-targeted radiopharmaceuticals hold promise for the treatment of advanced-stage EOC.

Background: Selective internal radiation therapy (SIRT) with yttrium-90 (Y-90) microspheres is an established locoregional treatment for early- to intermediate-stage hepatocellular carcinoma (HCC). While both resin and glass microspheres are widely used, their comparative effectiveness and safety in lobar infusion remain unclear. This study aimed to compare the effectiveness and safety of resin versus glass microspheres in patients with early- to intermediate-stage HCC undergoing lobar Y-90 SIRT.

Results: A retrospective single-center analysis was conducted on 37 consecutive patients with early- to intermediate-stage HCC who underwent lobar Y-90 SIRT (resin: n = 22; glass: n = 15). Baseline characteristics were comparable between the two groups, except for age (glass: 64 ± 6.9 years vs. resin: 69 ± 7.1 years; P = 0.036). Radiation doses to the tumour and non-tumoural liver were comparable between the resin and glass groups (all P > 0.05). Patients treated with resin microspheres showed significantly longer progression-free survival (PFS) (median 9.3 vs. 6.4 months; P = 0.043) and overall survival (OS) (median 16.4 vs. 12.0 months; P = 0.035), and also demonstrated higher overall response rates, compared with those treated with glass microspheres. Univariate Cox regression identified resin microsphere use as a significant predictor of improved PFS and OS, while higher Barcelona Clinic Liver Cancer (BCLC) stage, multifocal disease, and tumour burden ≥ 25% were associated with worse survival (all P < 0.05). Fine-Gray competing risk regression, accounting for post-SIRT treatments as competing events, further confirmed the OS benefit of resin microspheres compared with glass microspheres (subdistribution hazard ratio [SHR] = 0.35; P = 0.011). Subgroup analysis demonstrated that the survival advantage of resin microspheres was particularly evident in patients with a maximum tumour diameter ≥ 5 cm (PFS: hazard ratio [HR] = 0.258, 95% confidence interval [CI]: 0.073-0.914; OS: HR = 0.111, 95% CI: 0.013-0.962). Safety outcomes were comparable between the two groups, with no significant differences in short- to long-term adverse events graded according to the Common Terminology Criteria for Adverse Events version 5.0, or in laboratory changes at 4-month follow-up (all P > 0.05).

Conclusions: In lobar Y-90 SIRT for early-to intermediate-stage HCC, resin microspheres were associated with improved outcomes without increased toxicity compared to glass microspheres, particularly in patients with large tumours. These findings support a potential benefit of resin versus glass microspheres in lobar SIRT and warrant prospective validation in larger cohorts.

Background: [¹⁸F]FDG PET-CT scan has a lower sensitivity in imaging of indolent non-Hodgkin's Lymphoma (NHL.) We aimed at identifying a threshold of clinical/pathological indicators which would independently predict [¹⁸F]FDG PET-CT scan positivity. For this purpose, we used a retrospective real-world cohort of NHL patients and then validated this criterion on [¹⁸F]FDG and [⁶⁸Ga]Pentixafor scans in a prospective indolent NHL cohort.

Results: In the retrospective real-world cohort of NHL, Ki67 was identified as an independent factor that influenced [¹⁸F]FDG uptake (r = 0.701). The cutoff value for Ki67 was 36.5% with a maximum area under the curve (AUC) of 0.811 and a Youden index of 0.494 for predicting [¹⁸F]FDG imaging positivity. The sensitivity of [¹⁸F]FDG PET in retrospective NHL cohort was only 65.2% (101/155) which further decreased to 46.3% in patients with Ki 67 ≤ 35%. In the prospective comparison of patients with Ki67 ≤ 35%, [⁶⁸Ga]Pentixafor had a higher sensitivity (80.6% (29/36)) than that of [¹⁸F]FDG PET-CT scan (30.6% (11/36)). However, in patients with Ki67 > 35%, both the imaging modalities had similar sensitivities of 60% (3/5).

Conclusion: A Ki67 of 35% was shown to be a promising threshold criterion for choosing between [¹⁸F]FDG or [⁶⁸Ga]Pentixafor PET tracer in patients with indolent NHL.

Trial registration: A Study Evaluating the Value of 68Ga-Pentixafor PET Imaging in the Staging of Hematological Tumor, and Comparing it With 18 F-FDG PET/CT Imaging, NCT06834412. Registered 13 February 2025 - Retrospectively registered, https://register.

Clinicaltrials: gov/prs/beta/studies/S000FBBP00000062.

Background: Accurate pre- and intraoperative assessment of disease extent is crucial for curative treatment of colorectal liver metastases (CRLM) and primary colorectal cancer (pCRC). Tumour-targeted nuclear imaging can enhance pre- and postoperative tumour staging, while tumour-specific fluorescence-guided surgery can improve intraoperative visualization. However, validated targets remain limited, particularly for CRLM. This study aimed to identify and validate novel molecular targets for CRLM using a data-driven approach. Additional objectives included pCRC target expression and evaluating target expression in neoadjuvant-treated patients.

Results: Using a data-driven RNA-based discovery approach (Euretos), candidate targets for colorectal liver metastases were identified. Of these, the six highest-ranking targets-CEACAM5, EPCAM, CEACAM6, MUC13, FXYD3, and CDH17-were selected for validation through immunohistochemistry (IHC). Semi-automated image analysis quantified IHC staining intensity (0-100) for tumour epithelium and background on a per-pixel basis. A patient's staining pattern was regarded as positive if mean tumour epithelium scored positive (>25), background negative (<25) and tumour epithelium >25 points higher than background, referred to as relative positive expression. The proportion of CRLM samples showing relative positive expression was 79% for CEACAM5, 45% for EPCAM, 80% for CEACAM6, 24% for MUC13, 58% for FXYD3, and 22% for CDH17. CEACAM5/CEACAM6 combined positivity reached 90% (either one positive), showing that targeting both markers enables molecular imaging in nearly the entire population. Staining intensities were similar in pCRC epithelium (P >0.05). Neoadjuvant-treated CRLM exhibited higher expression for all targets.

Conclusion: Using a novel data-driven approach, six potential imaging targets were successfully identified and validated. CEACAM5 and CEACAM6 emerged as strong targets that, regardless of neoadjuvant therapy, covered nearly the entire CRLM population-supporting their further probe development and clinical translation.

Background: Sodium [¹⁸F]Fluoride Positron Emission Tomography (Na[¹⁸F]F PET) is a promising imaging biomarker for evaluating bone metabolism in spondyloarthritis (SpA) and other bone affecting diseases. Accurate quantification of tracer uptake is essential for assessing disease activity and treatment response. This study aimed to determine optimal simplified metrics for Na[¹⁸F]F uptake and evaluate their performance compared to net influx rate (K_i).

Results: A prospective study included 54 SpA patients undergoing Na[¹⁸F]F PET/CT scans at baseline and after 12 weeks of therapy. Dynamic PET in combination with venous blood sampling was analyzed to derive kinetic parameters, including K_i in 43 scans that included pathological uptake in the dynamic field of view. Semi-quantitative standardized uptake values (SUVs) corrected body weight (BW), lean body mass (LBM), body surface area (BSA) and skeletal volume (SV) were compared and correlations between K_i and SUVs were assessed cross-sectionally and longitudinally. Based on analysis of the blood sample data, there was a significant difference between SUV corrected for BW between patients who weighted more and less than 85 kg (p < 0.01 at all sample moments). When LBM or SV was used, this difference disappeared (p > 0.05). There was a significant correlation between K_i and various SUV-metrics, with SUV_peak-LBM at 25-30 min yielding the highest correlation both cross-sectionally (R² = 0.77, p < 0.01), and longitudinally (R² = 0.54, p < 0.01).

Conclusions: Na[¹⁸F]F uptake quantification of lesions in the axial skeleton of SpA patients can be performed cross-sectionally and longitudinally with simplified uptake measures, particularly SUV_peak, normalized using LBM or SV. This offers a more reliable approach to evaluating disease activity and treatment responses compared to BW.

Background: Pneumoconiosis, characterized by dust-induced pulmonary fibrosis, lacks reliable methods to assess fibrotic activity. This study aimed to monitor fibroblast activation and identify activated pulmonary fibrosis for early diagnosis and anti-fibrotic therapy response by ¹⁸F-fibroblast activation protein inhibitors (FAPI) positron emission tomography/computed tomography (PET/CT) in pneumoconiosis.

Methods: A single-center prospective clinical study was conducted on 6 pneumoconiosis patients and 4 healthy control individuals. The uptake of ¹⁸F-FAPI in the pulmonary fibrosis areas of participants and its correlation with pulmonary diffusion function were analyzed. Sprague-Dawley rat experiments were performed on three groups including pneumoconiosis model, pirfenidone-treated, and normal control groups. ¹⁸F-FAPI and ¹⁸F-fluoro-D-glucose (FDG) PET/CT, histopathologic, and hematological analysis were assessed monthly from modeling until 6 months.

Results: In our preliminary cohort, compared to the controls, the ¹⁸F-FAPI uptake in fibrotic areas of pneumoconiosis patients was higher, and a strong negative correlation with the diffusing function was observed (r = -0.929, P = 0.022). In the pneumoconiosis model, ¹⁸F-FAPI activity peaked one month earlier than relative collagen content (%) in Masson trichrome staining and the level of connective tissue growth factor in plasma, an indicator reflecting the fibroblast activation. The uptake of ¹⁸F-FAPI in the pirfenidone-treated group significantly decreased compared to the pneumoconiosis group. Additionally, in pneumoconiosis rats, ¹⁸F-FDG uptake peaked at Month 3, correlating with progressive inflammation (granuloma formation, elevated interleukin-6 [IL-6]/tumor necrosis factor-α [TNF-α]), while pirfenidone showed timepoint-specific metabolic reduction, no significant difference in the overall mean standardized uptake value (SUVmean) was observed.

Conclusions: ¹⁸F-FAPI PET/CT imaging may hold promise for identifying active pulmonary fibrosis and monitoring its progression in pneumoconiosis, suggesting a potential clinical opportunity for targeted anti-fibrotic treatment. These preliminary findings warrant further investigation in larger studies.