Clinical performance of [⁶⁸Ga]Ga-DOTA-FAPI-04 PET/CT in detecting recurrent disease in medullary thyroid carcinoma: a comparative analysis with [¹⁸F]F-FDG and [⁶⁸Ga]Ga-DOTATATE PET/CT, alongside identification of suitable candidates for targeted radionuclide therapy.

Abstract

To evaluate and compare the diagnostic performance of [⁶⁸Ga]Ga-DOTA-FAPI-04 with [¹⁸F]F-FDG and [⁶⁸Ga]Ga-DOTATATE PET/CT for detecting recurrent disease in patients with medullary thyroid carcinoma (MTC) and additionally evaluate their role for prognostication and theranostics in management of MTC. In this prospective single-centre study, 56 patients with suspected recurrent MTC underwent [⁶⁸Ga]Ga-DOTA-Fibroblast activation protein inhibitor (FAPI)-04, [¹⁸F]F-FDG, and [⁶⁸Ga]Ga-DOTATATE PET/CT. The primary endpoint was patient-based diagnostic accuracy for recurrent disease. Secondary endpoints included lesion-based detection rates across pre-defined anatomical regions, correlation with biochemical and clinicopathological parameters, prognostic assessment for progression-free survival, and a novel exploratory FAPI-SSTR Theranostic (FAST) score was developed to guide personalized radiopharmaceutical therapy (RPT). [⁶⁸Ga]Ga-DOTA-FAPI-04 PET/CT demonstrated higher sensitivity 95.92% and accuracy 94.64% compared to [¹⁸F]F-FDG-PET/CT (sensitivity: 89.80%, accuracy: 89.29%) and [⁶⁸Ga]Ga-DOTATATE (sensitivity: 77.55%, accuracy: 76.79%) on patient-based analysis for detecting recurrent disease. [⁶⁸Ga]Ga-DOTA-FAPI-04 was showed high detection rates for disease recurrence in mediastinal nodal (91.9%), liver (91.7%), and skeletal (86.5%) metastases.[⁶⁸Ga]Ga-DOTA-FAPI-04 uptake was associated with a modestly shorter mean progression-free survival and altered clinical management in 35.7% of total patients. Additionally, the pre-defined exploratory FAST scoring system stratified 34 patients (60.7%) for [¹⁷⁷Lu]Lu-FAPI-RPT, 8 (14.3%) for [¹⁷⁷Lu]Lu-DOTATATE PRRT, and 9 (16.1%) for either or combined RPT. [⁶⁸Ga]Ga-DOTA-FAPI-04 PET/CT showed higher diagnostic accuracy for the identification of recurrent MTC over standard [¹⁸F]F-FDG and [⁶⁸Ga]Ga-DOTATATE PET/CT, with higher regional detection rates for liver and osteoblastic skeletal metastases. Furthermore, while the exploratory FAST score provides a framework for patient stratification and personalizing targeted theranostic strategies, it requires future validation through larger multicentre trials prior to clinical adoption.