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

Abstract

Medullary thyroid carcinoma (MTC) arises from thyroid C-cells and secretes calcitonin. Conventional anatomical imaging frequently fails to identify small lesions and biochemically recurrent tumors, necessitating phenotype-guided positron emission tomography (PET) evaluation. This article summarizes three mainstream PET tracers - ¹⁸F-fluorodihydroxyphenylalanine (FDOPA), gallium-68-labelled somatostatin receptor (SSTR) analogues, and ¹⁸F-fluorodeoxyglucose (FDG) - across initial staging, biochemical recurrence, and restaging settings. Meta-analyses confirm ¹⁸F-FDOPA achieves the highest sensitivity for recurrent or persistent MTC, with detection improved by elevated calcitonin levels and shorter doubling times. Increased FDG uptake indicates aggressive, dedifferentiated disease, while SSTR PET shows lower overall detection rates in MTC but remains valuable for assessing bone involvement and selecting candidates for PRRT. Current guidelines recommend a biology-driven imaging strategy: ¹⁸F-FDOPA is the first-choice tracer for biochemical recurrence when available; FDG is reserved for high-grade progressive disease, and SSTR PET guides pre-PRRT evaluation. Routine PET is not recommended for initial staging, though selective use is reasonable in high-risk patients combined with conventional imaging. This study proposes an evidence-based imaging algorithm for radiologists according to serum markers, tracer advantages and theranostic needs. Further prospective trials, standardized SSTR thresholds and investigations of novel tracers are still required to fill existing research gaps.

Keywords: Medullary thyroid carcinoma; Positron emission tomography; Fluorodihydroxyphenylalanine; Fluorodeoxyglucose; Somatostatin receptor; Calcitonin; Peptide receptor radionuclide therapy; Theranostics

Core Tip: Selecting the right positron emission tomography tracer in medullary thyroid carcinoma depends on tumour biology. This article synthesizes evidence from five databases indicating that fluorodihydroxyphenylalanine remains the most sensitive tracer for recurrent disease, whereas fluorodeoxyglucose better captures aggressive, dedifferentiated tumours. Somatostatin receptor imaging, though less sensitive overall, is indispensable for identifying candidates for peptide receptor radionuclide therapy. We propose an expert-informed, biology-guided algorithm linking biomarker kinetics to tracer choice and highlight cholecystokinin-2 receptor and fibroblast activation protein as promising emerging targets.