Positron emission tomography tracers in medullary thyroid carcinoma: Current evidence and emerging targets

Table 1 Comparative diagnostic performance of positron emission tomography tracers in recurrent medullary thyroid carcinoma

Tracer	Ref.	Patient-based detection rate (sensitivity)	Lesion-based detection rate	Key correlate/finding
18F-FDOPA	Treglia et al[4], 2012	66% (pooled)	71% (pooled)	Sensitivity rises to 86% with Ctn > 1000 pg/mL
	Lee et al[5], 2020	Highest among 5 tracers (network meta-analysis)	N/A	Ranked 1 for patient-level detection
	Zhang et al[6], 2024	95% (single-centre cohort, n = 109)	N/A	High specificity (93%) and accuracy (94%)
18F-FDG	Cheng et al[13], 2012	68-69% (pooled)	N/A	General performance in recurrent/metastatic MTC
	Treglia et al[14], 2012	75% (with Ctn > 1000 pg/mL)	N/A	Sensitivity rises to 91% with CEA DT < 24 months
	Verbeek et al[15], 2012	77% positivity in patients with Ctn DT < 24 months	N/A	Strong correlation with aggressive disease
68Ga-SSTR	Treglia et al[17], 2017	63.5% (pooled)	N/A	Lower than FDOPA; comparable to FDG
	Hayes et al[18], 2021	26% show sufficient uptake for PRRT	N/A	Highlights limited PRRT eligibility
	Castroneves et al[19], 2018	100% for bone metastases	N/A	Superior to bone scintigraphy (44%) for bone lesions

This table summarizes the key diagnostic performance metrics from foundational meta-analyses and large cohort studies for the three main tracers. ¹⁸F-FDOPA: ¹⁸F-fluorodihydroxyphenylalanine; ¹⁸F-FDG: ¹⁸F-fluorodeoxyglucose; ⁶⁸Ga-SSTR: Gallium-68-labelled somatostatin receptor; Ctn: Calcitonin; DT: Doubling time; N/A: Not applicable; PRRT: Peptide receptor radionuclide therapy; MTC: Medullary thyroid carcinoma; CEA: Carcinoembryonic antigen; FDG: Fluorodeoxyglucose; FDOPA: Fluorodihydroxyphenylalanine.

Table 2 Organ-specific detection sensitivities of positron emission tomography tracers in metastatic medullary thyroid carcinoma

Metastatic site	18F-FDOPA	68Ga-SSTR	18F-FDG	11C-methionine	Best performing tracer
Neck/Lymph nodes	85.7%	68.2%	61.5%	83.3%	18F-FDOPA
Liver	90.9%	75.0%	66.7%	88.9%	18F-FDOPA
Bone	84.2%	94.7%	78.9%	89.5%	68Ga-SSTR
Lung	78.6%	71.4%	71.4%	92.9%	¹¹C-methionine

This table, based on the network meta-analysis by Li et al[10], provides a clear comparison of which tracer performs best for specific metastatic sites. ¹¹C-methionine has limited clinical availability. ¹⁸F-FDOPA: ¹⁸F-fluorodihydroxyphenylalanine; ¹⁸F-FDG: ¹⁸F-fluorodeoxyglucose; ⁶⁸Ga-SSTR: Gallium-68-labelled somatostatin receptor.

Table 3 Summary of key evidence for emerging positron emission tomography tracers in metastatic medullary thyroid carcinoma

Tracer platform	Target	Key advantage(s)	Ref.	Key finding(s)
CCK2R/minigastrin	CCK2R	Expressed in about 92% of MTCs	Günther et al[24], 2024	Proof-of-concept PET imaging with high tumour uptake (SUVmax 7.4)
		Complete theranostic platform (68Ga, 177Lu, 225Ac)	Holzleitner et al[25], 2025	Preclinical 225Ac alpha therapy showed 4.5-fold survival benefit
FAPI	FAP	Targets tumour stroma, not tumour cells	Kong et al[27], 2025	Head-to-head vs FDG: 98% vs 66% detection rate; SUVmax 11.7 vs 2.6; changed management in 32% of patients
		Very high tumour-to-background contrast
Novel SSTR	SSTR	18F-labelling overcomes 68Ga generator limitations	Kunte et al[20], 2025	18F-SiTATE PET burden correlated with calcitonin levels (r = 0.771)
		Improved logistics and potentially higher resolution

This table introduces the novel tracers, summarizing their target, key advantages, and the most impactful early clinical findings. CCK2R: Cholecystokinin-2 receptor; MTCs: Medullary thyroid carcinomas; FAPI: Fibroblast activation protein inhibitor; FAP: Fibroblast activation protein; SSTR: Somatostatin receptor; SUVmax: Standardised uptake value maximum; FDG: Fluorodeoxyglucose; ¹⁸F-SiTATE: 18F-labelled silicon-containing somatostatin receptor ligand; PET: Positron emission tomography; ⁶⁸Ga: Gallium-68; ¹⁷⁷Lu: Lutetium-177; ²²⁵Ac: Actinium-225.