2026-07-01 | 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.
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.
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2026-06-25 | Long-term outcomes in medullary thyroid cancer patients treated with [177Lu]Lu-DOTAGA.FAPi dimer therapy.
Fibroblast activation protein (FAP)-targeted radionuclide therapy is a promising approach for patients with advanced or metastatic medullary thyroid carcinoma (MTC). This study evaluates efficacy, safety, and survival outcomes of [177Lu]/[225Ac]-DOTAGA.Glu.(FAPi)₂ therapy in this population. Nineteen patients with progressive MTC were treated with either [¹⁷⁷Lu]Lu-DOTAGA.Glu.(FAPi)₂ or [²²⁵Ac]Ac-DOTAGA.Glu.(FAPi)₂, receiving a median of 5 cycles. The median cumulative activity administered was 20.3 GBq (Lu) and 6.66 MBq (Ac) and the median follow-up was 21 months. Of the 17 evaluable patients, radiological response was assessed in 15 patients using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). The analysis demonstrated a partial response (PR) in 33% of patients, stable disease (SD) in 47%, and progressive disease (PD) in 20%, resulting in a disease control rate (DCR) of 80%. Positron emission tomography response criteria in solid tumors (PERCIST) evaluation (n = 15) showed 47% PR, 40% SD, and 13% PD. Biochemical response was evaluable in 14 patients: 64.2% showed stable or decreasing tumor markers. Median calcitonin doubling time was 6.7 months. Clinical progression occurred in 2 patients. Median PFS was 26 months; median OS was 42 months. No statistically significant difference in OS was observed between progression and non-progression groups (log-rank p-0.758). No Grade 4 or life-threatening toxicities were observed. Only two patients experienced Grade 3 adverse events-one with elevated alkaline phosphatase and one with worsening anemia. All other hematologic and biochemical toxicities were limited to Grade 1-2. [177Lu]/[225Ac]-DOTAGA.Glu.(FAPi)₂ therapy shows encouraging disease control, acceptable safety, and preliminary efficacy signals such as increased survival in the treated patients of advanced MTC.
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2026-06-16 | Multiple endocrine neoplasia type 2: From molecular genetics to precision therapy.
Multiple endocrine neoplasia type 2 is an autosomal dominant hereditary syndrome characterized by a predisposition to medullary thyroid carcinoma and pheochromocytoma. The discovery of the RET proto-oncogene as the molecular driver of this syndrome has revolutionized the management of this disease, enabling presymptomatic diagnosis of medullary thyroid carcinoma, which leads to prophylactic thyroidectomy, screening for pheochromocytomas, and the discovery of systemic therapies that control advanced disease. This article reviews genotype-phenotype correlations, clinical manifestations, and current therapeutic strategies, including the use of selective tyrosine kinase inhibitors. In addition, we propose an algorithm for the treatment of advanced medullary thyroid carcinoma and metastatic pheochromocytoma.
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