Masao Watanabe

Objective FAPI-PET/CT exhibits high tumor uptake and low background accumulation, enabling high-sensitivity tumor detection. We compared the diagnostic performance of ⁶⁸ Ga-FAPI-46 PET/CT plus contrast-enhanced CT (CE-CT), ¹⁸F-FDG PET/CT plus CE-CT, and standalone CE-CT in patients with various malignancies. Methods 232 patients underwent ⁶⁸ Ga-FAPI-46 PET/CT,¹⁸F-FDG PET/CT, and CE-CT each within 4 weeks. Detection rates were assessed by a blinded reader, with ≥ 2 weeks between scans of the same patient to avoid recall bias. A sub-analysis of diagnostic performance was performed for 490 histopathologically validated lesions. Detection rates were compared using McNemar’s test. Results Lesion-based detection rates in ⁶⁸ Ga-FAPI-46 PET/CT plus CE-CT, ¹⁸F-FDG PET/CT plus CE-CT, and CE-CT alone were 91.2% (1540/1688), 82.5% (1393/1688) and 60.2% (1016/1688). The detection rates were significantly higher for ⁶⁸ Ga-FAPI-46 PET/CT plus CE-CT than for ¹⁸F-FDG PET/CT plus CE-CT (p < 0.02 for primary lesions and p < 0.001 for total, abdominopelvic nodal, liver and other visceral lesions) and CE-CT (p < 0.0001 for total, primary, cervicothoracic nodal, abdominopelvic nodal, liver, other visceral, and bone lesions). In the sub-analysis, sensitivity, specificity, positive and negative predictive value, and accuracy were 61.3%, 96.7%, 81.4%, 91.4% and 90.0% for ⁶⁸ Ga-FAPI-46 PET/CT plus CE-CT, 57.0%, 95.7%, 75.7%, 90.5% and 88.4% for ¹⁸F-FDG PET/CT plus CE-CT, and 51.6%, 97.2%, 81.4%, 89.6% and 88.6% for CECT, respectively. Conclusions ⁶⁸ Ga-FAPI-46 PET/CT plus CE-CT demonstrates a higher tumor detection rate than ¹⁸F-FDG PET/CT plus CE-CT and CE-CT in a diverse spectrum of malignancies, especially for primary, abdominopelvic nodal, liver, and other visceral lesions. Further studies on which entities draw particular benefit from ⁶⁸ Ga-FAPI-46 PET/CT are warranted to aid appropriate diagnostic workup. Trial registration A total of N = 232 patients were analyzed. Of these, N = 50 patients were included in a prospective interventional trial (NCT05160051), and N = 175 in a prospective observational trial (NCT04571086) for correlation and clinical follow-up of PET findings; N = 7 patients were analyzed retrospectively.

The benefit of multicompartment dosimetry in the radioembolization of neuroendocrine neoplasms is not firmly established. We retrospectively assessed its potential with patient outcome. Methods: Forty-three patients were eligible. The association of mean absorbed dose (MAD) for tumors and treatment response was tested per lesion with a receiver operating characteristic curve analysis, and the association of MAD with progression-free survival (PFS) and overall survival was tested per patient using uni- and multivariate Cox regression analyses. Results: The area under the curve for treatment response based on MAD was 0.79 (cutoff, 196.6 Gy; P < 0.0001). For global PFS, grade (grade 2 vs. 1: hazard ratio [HR], 2.51; P = 0.042; grade 3 vs. 1: HR, 62.44; P < 0.001), tumor origin (HR, 6.58; P < 0.001), and MAD (HR, 0.998; P = 0.003) were significant. For overall survival, no prognostic parameters were significant. Conclusion: In line with prior publications, a MAD of more than 200 Gy seemed to favor treatment response. MAD was also associated with PFS and may be of interest for radioembolization planning for neuroendocrine neoplasm patients. Visual Abstract

Tumoral fibroblast activation protein expression is associated with proliferation and angiogenesis and can be visualized by PET/CT. We examined the prognostic value of [⁶⁸Ga]Ga-fibroblast activation protein inhibitor (FAPI) (⁶⁸Ga-FAPI)–46 PET/CT for different tumor entities in patients enrolled in 2 prospective imaging studies (NCT05160051, n = 30; NCT04571086, n = 115). Methods: Within 4 wk, 145 patients underwent ⁶⁸Ga-FAPI-46 and [¹⁸F]FDG (¹⁸F-FDG) PET/CT. The association between overall survival (OS) and sex, age, tumor entity, total lesion number, highest SUV_max, and the presence of each nodal, visceral, and bone metastasis was tested using univariate Cox regression analysis. Multivariate analyses were performed for prognostic factors with P values of less than 0.05. Results: In the univariate analysis, shorter OS was associated with total lesion number and the presence of nodal, visceral, and bone metastases on ⁶⁸Ga-FAPI-46 PET/CT (hazard ratio [HR], 1.06, 2.18, 1.69, and 2.05; P < 0.01, < 0.01, = 0.04, and = 0.02, respectively) and ¹⁸F-FDG PET/CT (HR, 1.05, 2.31, 1.76, and 2.30; P < 0.01, < 0.01, = 0.03, and < 0.01, respectively) and with SUV_max on ⁶⁸Ga-FAPI-46 PET/CT (HR, 1.03; P = 0.03). In the multivariate analysis, total lesion number on ⁶⁸Ga-FAPI-46 PET/CT was an independent risk factor for shorter OS (HR, 1.05; P = 0.02). In patients with pancreatic cancer, shorter OS was associated with total lesion number on ⁶⁸Ga-FAPI-46 PET/CT (HR, 1.09; P < 0.01) and bone metastases on ¹⁸F-FDG PET/CT (HR, 31.39; P < 0.01) in the univariate analysis and with total lesion number on ⁶⁸Ga-FAPI-46 PET/CT (HR, 1.07; P = 0.04) in the multivariate analyses. In breast cancer, total lesion number on ⁶⁸Ga-FAPI-46 PET/CT (HR, 1.07; P = 0.02), as well as bone metastases on ¹⁸F-FDG PET/CT (HR, 9.64; P = 0.04), was associated with shorter OS in the univariate analysis. The multivariate analysis did not reveal significant prognostic factors. In thoracic cancer (lung cancer and pleural mesothelioma), the univariate and multivariate analyses did not reveal significant prognostic factors. Conclusion: Disease extent on ⁶⁸Ga-FAPI-46 PET/CT is a predictor of short OS and may aid in future risk stratification by playing a supplemental role alongside ¹⁸F-FDG PET/CT. Visual Abstract

Background: Texture features reflecting tumour heterogeneity enable us to investigate prognostic factors. The R package ComBat can harmonize the quantitative texture features among several positron emission tomography (PET) scanners. We aimed to identify prognostic factors among harmonized PET radiomic features and clinical information from pancreatic cancer patients who underwent curative surgery. Methods: Fifty-eight patients underwent preoperative enhanced dynamic computed tomography (CT) scanning and fluorodeoxyglucose PET/CT using four PET scanners. Using LIFEx software, we measured PET radiomic parameters including texture features with higher order and harmonized these PET parameters. For progression-free survival (PFS) and overall survival (OS), we evaluated clinical information, including age, TNM stage, and neural invasion, and the harmonized PET radiomic features based on univariate Cox proportional hazard regression. Next, we analysed the prognostic indices by multivariate Cox proportional hazard regression (1) by using either significant (p < 0.05) or borderline significant (p = 0.05–0.10) indices in the univariate analysis (first multivariate analysis) or (2) by using the selected features with random forest algorithms (second multivariate analysis). Finally, we checked these multivariate results by log-rank test. Results: Regarding the first multivariate analysis for PFS after univariate analysis, age was the significant prognostic factor (p = 0.020), and MTV and GLCM contrast were borderline significant (p = 0.051 and 0.075, respectively). Regarding the first multivariate analysis of OS, neural invasion, Shape sphericity and GLZLM LZLGE were significant (p = 0.019, 0.042 and 0.0076). In the second multivariate analysis, only MTV was significant (p = 0.046) for PFS, whereas GLZLM LZLGE was significant (p = 0.047), and Shape sphericity was borderline significant (p = 0.088) for OS. In the log-rank test, age, MTV and GLCM contrast were borderline significant for PFS (p = 0.08, 0.06 and 0.07, respectively), whereas neural invasion and Shape sphericity were significant (p = 0.03 and 0.04, respectively), and GLZLM LZLGE was borderline significant for OS (p = 0.08). Conclusions: Other than the clinical factors, MTV and GLCM contrast for PFS and Shape sphericity and GLZLM LZLGE for OS may be prognostic PET parameters. A prospective multicentre study with a larger sample size may be warranted.

Purpose Flexible positron emission tomography (fxPET) employing a non-local means reconstruction algorithm was designed to fit existing magnetic resonance imaging (MRI) systems. We aimed to compare the qualitative and quantitative performance of fxPET among fxPET with MR-based attenuation correction (MRAC), fxPET with CT-based attenuation correction (CTAC) using CT as a part of WB PET/CT, and whole-body (WB) PET/CT. Procedures Sixteen patients with suspected head and neck cancer underwent 2-deoxy-2-[¹⁸F]fluoro-d-glucose WB PET/CT scans, followed by fxPET and 3 T MRI scans. Phantom data were compared among the three datasets. For registration accuracy, we measured the distance between the center of the tumor determined by fxPET and that in MRI. We compared image quality, detection rates, and quantitative values including maximal standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor-to-muscle ratio (TMR) among the three datasets. Results The phantom data in fxPET, except the percent contrast recoveries of 17-mm and 22-mm hot spheres, were inferior to those in WB PET/CT. The mean registration accuracy was 4.4 mm between fxPET using MRAC and MRI. The image quality was comparable between two fxPET datasets, but significantly inferior to WB PET/CT (p < 0.0001). In contrast, detection rates were comparable among the three datasets. SUVmax was significantly higher, and MTV and TLG were significantly lower in the two fxPET datasets compared with the WB PET/CT dataset (p < 0.005). There were no significant differences in SUVmax, MTV, and TLG between the two fxPET datasets or in TMR among the three datasets. All quantitative values had significantly positive correlations. Conclusions Compared with WB PET/CT, the phantom data and image quality were inferior in fxPET. However, the results of the detection rates and quantitative values suggested the clinical feasibility of fxPET.

Aim: Aortic arch calcification (AoAC) on chest X-rays represents systemic atherosclerosis and it is associated with ischemic cardiovascular diseases. However, the relationship between ischemic stroke and AoAC has yet to be fully elucidated. Methods: Patients with acute ischemic stroke who were undergoing chest X-ray, blood, and brain magnetic resonance imaging (MRI) examinations were prospectively studied. The extent of AoAC on chest X-ray was divided into four grades (0-3). Clinical characteristics, biochemical findings, white matter lesions on MRI, and AoAC extent were assessed in each stroke subtype, and the factors associated with AoAC were investigated. Results: A total of 175 patients (age, 70±13 years; 115 men) were enrolled in the study. According to the Trial of Org 10172 in Acute Stroke Treatment classification with minor modification, 33 patients (19%) had small artery occlusion (SAO), 42 (24%) had large artery atherosclerosis, 49 (28%) had cardioembolism, 24 (14%) had stroke with other determined etiologies, and 27 (17%) had stroke with undetermined etiologies. Compared to other stroke subtypes, the extent of AoAC was independently correlated with SAO (all p＜0.05). Age (odds ratio [OR]: 1.14, 95% confidence interval [CI]: 1.08 to 1.19, p＜0.001), hypertension, (OR: 3.44, 95% CI: 1.23 to 9.66, p=0.019), diabetes mellitus (OR: 2.19, 95% CI: 0.99 to 4.85, p=0.054), white matter lesions (OR: 1.54, 95% CI: 1.00 to 2.36, p=0.048), and SAO (OR: 1.38, 95% CI: 1.02 to 1.89, p=0.040) were significantly associated with AoAC. Conclusions: Age, hypertension, cerebral small artery disease, and possibly diabetes mellitus appear to be closely associated with AoAC in patients with acute ischemic stroke.