Evaluation of [68Ga]Ga-FAPI PET/CT-derived parameters in thyroid nodules with emphasis on indeterminate cytology

Abstract

Objectives: To evaluate the diagnostic performance of [68Ga]Ga-FAPI PET/CT-derived metabolic parameters in thyroid nodules and their association with cytological risk stratification, with particular emphasis on indeterminate nodules.

Methods: Forty patients with 53 thyroid nodules who underwent [68Ga]Ga-FAPI PET/CT were prospectively analysed. Maximum standardized uptake value (SUVmax) and tumour-to-background ratio (TBR) were calculated for each nodule. Ultrasound-based malignancy classification (USG-BM) and Bethesda cytology categories were recorded. Comparisons between benign and malignant nodules were performed in the overall cohort (Bethesda I-VI) and within the Bethesda III-IV subgroup. Multivariable logistic regression was used to identify independent predictors of malignancy. Diagnostic performance was assessed using receiver operating characteristic analysis.

Results: In the overall cohort, SUVmax and TBR were significantly higher in malignant nodules than in benign nodules (P < .01). In multivariable analysis, TBR showed a stronger independent association with malignancy, whereas USG-BM was not independently predictive. Within the Bethesda III-IV subgroup, SUVmax and TBR did not differ significantly in univariable analyses; however, TBR demonstrated a borderline independent association with malignancy in multivariable analysis (P = .058). Maximum standardized uptake value and TBR values were significantly higher in Bethesda V-VI nodules compared with Bethesda III-IV nodules (both P < .001). Receiver operating characteristic (ROC) analysis demonstrated good discriminative performance for both parameters, with TBR yielding a higher area under the curve and high negative predictive values.

Conclusion: [68Ga]Ga-FAPI PET/CT-derived metabolic parameters, particularly TBR, show promising diagnostic performance for thyroid nodule characterization. High negative predictive values suggest a potential complementary role for excluding malignancy, especially in indeterminate nodules. Further multicentre studies are warranted.

Advances in knowledge: [68Ga]Ga-FAPI PET/CT-derived metabolic parameters were higher in malignant thyroid nodules compared with benign lesions. These findings suggest that FAPI PET/CT may provide complementary functional information in nodules with indeterminate cytology.

Keywords: Bethesda; FAPI PET; TIRADS; risk stratification; thyroid nodules.