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Purpose: To investigate the influence of germline succinate dehydrogenase (SDHx) pathogenic variants on 6-[ 18 F]-fluoro-3,4-dihydroxyphenylalanine ( 18 F-DOPA) Positron Emission Tomography (PET) radiomic signature of head and neck paragangliomas (HNPGLs)., Methods: Forty-seven patients (20 SDH pathogenic variants carriers) harboring 55 HNPGLs were retrospectively included. HNPGLs were delineated using Nestle adaptive threshold. 128 radiomic features were extracted and harmonized to correct for batch effects. Principal Component Analysis (PCA) was performed to remove redundancy and avoid collinearity. The most representative feature of each component was tested with multivariate stepwise logistic binary regression analysis (LBRA) to identify variables predictive of genetic status., Results: 18 F-DOPA Positron Emission Tomography/Computed Tomography (PET/CT) detected 28/29 carotid body HNPGLs, 23/23 jugulotympanic HNPGLs, and 4/4 vagal HNPGLs. SUVmax was significantly higher in SDH-related HNPGLs (p = 0.003). PCA allowed identification of 4 Components. The most representative variables of Component 1 and 2 (including intensity and intensity-related textural features, and not intensity-related textural features, respectively) were Intensity-based (IB)-SUVmedian and Grey Level Run Length Matrix-Long Run Low Gray Level Emphasis (GLRLM-LRLGLE). SDHx HNPGLs exhibited higher activity scores and more homogeneous texture. At patient level, SDHx cases showed significantly higher IB-SUVmedian values (p < 0.001), and lower GLRLM-LRLGLE than sporadic patients (p = 0.005). IB-SUVmedian was found to be an independent predictor of genetic status at lesion (71.0%) and patient level (77.8%)., Conclusion: The present study pioneers the application of 18 F-DOPA PET radiomics for HNPGLs, suggesting the influence of germline SDH pathogenic variants on 18 F-FDOPA uptake intensity and textural heterogeneity. Integrating radiomics with genetic data provides new insights into the correlation between PET features and underlying molecular dysregulation., Competing Interests: Declarations. Competing interests: The authors declare that they have no competing interests. Ethics approval and consent to participate: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Local institutional review board approved this retrospective study (IRB-2024-04), and all patients included gave a free and written informed consent for the use of the anonymous personal medical data extracted from their file for scientific or epidemiological purposes. Consent for publication: All patients included gave a free and written informed consent for the use of the anonymous personal medical data extracted from their file for scientific or epidemiological purposes., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Purpose: To investigate the [ 68 Ga]DOTATOC PET radiomic profile of head and neck paragangliomas (HNPGLs) and identify radiomic characteristics useful as predictors of succinate dehydrogenase genes (SDHx) pathogenic variants., Methods: Sporadic and SDHx HNPGL patients, who underwent [ 68 Ga]DOTATOC PET/CT, were retrospectively included. HNPGLs were analyzed using LIFEx software, and extracted features were harmonized to correct for batch effects and confronted testing for multiple comparison. Stepwise discriminant analysis was conducted to remove redundancy and identify best discriminating features. ROC analysis was used to define optimal cut-offs. Multivariate decision-tree analysis was performed using CHAID method., Results: 34 patients harboring 60 HNPGLs (51 SDHx in 25 patients) were included. Three sporadic and nine SDHx HNPGLs were metastatic. At stepwise discriminant analysis, both GLSZM-Zone Size Non-Uniformity (ZSNU, reflecting tumor heterogeneity) and IB-TLSRE (total lesion somatostatin receptor expression) were independent predictors of genetic status, with 96.4% of lesions and 91.6% of patients correctly classified after cross validation (p < 0.001). Among non-metastatic patients, GLSZM-ZSNU and IB-TLSRE were significantly higher in sporadic than SDHx HNPGLs (p < 0.001). No differences were revealed in metastatic patients. Decision-tree analysis highlights multifocality and IB-TLSRE as useful variables, correctly identifying 6/9 sporadic and 24/25 SDHx patients. Model failed to classify one SDHA and three sporadic patients (2 metastatic)., Conclusion: Radiomics features GLSZM-ZSNU and IB-TLSRE appear to reflect HNPGLs SDHx status and tumor behavior (metastatic vs. non-metastatic). If validated, especially IB-TLSRE might represent a simple and time-efficient radiomic index for SDHx variants early screening and prediction of tumor behavior in HNPGL cases., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)