*Review* **Next-Generation Molecular Imaging of Thyroid Cancer**

**Yuchen Jin 1,2,3,†, Beibei Liu 4,†, Muhsin H. Younis 5, Gang Huang 1, Jianjun Liu 1, Weibo Cai 5,6,\* and Weijun Wei 1,\***


**Simple Summary:** Molecular imaging utilizes radionuclides or artificially modified molecules to image particular targets or pathways which are important in the pathogenesis of a certain disease. Transporter-based probes like radioiodine and [18F]fluoro-D-glucose ([18F]FDG) are widely used for diagnosing thyroid cancer (TC) and predicting the prognosis thereafter. However, newly developed probes (peptide, antibody, nanoparticle probes, and aptamer) image the fine molecular changes involved in the pathogenesis of TC and enable target-specific diagnosis and treatment of TC. Furthermore, novel molecular probes have high specificity and sensitivity, imparting a high level of objectivity to the research areas of TC.

**Abstract:** An essential aspect of thyroid cancer (TC) management is personalized and precision medicine. Functional imaging of TC with radioiodine and [18F]FDG has been frequently used in disease evaluation for several decades now. Recently, advances in molecular imaging have led to the development of novel tracers based on aptamer, peptide, antibody, nanobody, antibody fragment, and nanoparticle platforms. The emerging targets—including HER2, CD54, SHP2, CD33, and more—are promising targets for clinical translation soon. The significance of these tracers may be realized by outlining the way they support the management of TC. The provided examples focus on where preclinical investigations can be translated. Furthermore, advances in the molecular imaging of TC may inspire the development of novel therapeutic or theranostic tracers. In this review, we summarize TC-targeting probes which include transporter-based and immuno-based imaging moieties. We summarize the most recent evidence in this field and outline how these emerging strategies may potentially optimize clinical practice.

**Keywords:** thyroid cancer; molecular imaging; theranostics; companion diagnostics; immunoPET
