18F-FAPI PET/CT Matches Ultrasound for Thyroid Tumors and Outperforms It for Neck Node Spread

A prospective imaging study has found that a preoperative PET scan using the tracer 18F-FAPI performs as well as ultrasound at identifying primary papillary thyroid tumors, and does a better job than ultrasound at confirming cervical lymph node metastases before surgery. The work, published in EJNMMI Research, enrolled 43 patients whose necks contained 58 thyroid lesions, 45 of which proved to be papillary thyroid carcinoma on pathology and 13 of which were benign.

The study evaluated FAP-targeted imaging, an approach that has been applied in differentiated thyroid cancer using either 68Ga or 18F labels. The study used an 18F-labeled FAPI agent for preoperative PET/CT imaging. According to the researchers, FAP-targeted imaging with either 68Ga or 18F labels has already been applied in differentiated thyroid cancer, particularly during postoperative follow-up, but its value in the preoperative setting had remained largely untested.

For primary thyroid lesions, the head-to-head comparison showed no statistically significant difference between 18F-FAPI PET/CT and ultrasound, with the two modalities achieving comparable diagnostic accuracy. For primary thyroid lesions, the study found no statistically significant difference in diagnostic accuracy between the two modalities (P>0.05). The finding suggests that in this cohort the PET tracer neither outperformed nor fell short of the standard approach when the question was simply whether a thyroid lesion was malignant.

The picture changed when the researchers turned to the neck. Among 23 cervical regional lymph node metastasis sites, 18F-FAPI imaging showed substantial agreement with the pathological results, quantified as a kappa of 0.603 with a P value below 0.001. Ultrasound, by contrast, reached only moderate consistency with pathology, with a kappa of 0.385 and a P value of 0.002. The kappa of 0.603 for 18F-FAPI imaging indicated substantial consistency with pathology, whereas the kappa of 0.385 for ultrasound indicated moderate consistency.

Beyond simple detection, the metabolic measurements extracted from the PET images carried information about metastatic behavior. The proportion of ipsilateral cervical lymph node metastases was significantly higher among thyroid lesions that took up the 18F-FAPI tracer than among tracer-negative lesions, at 60 percent versus 20 percent, a difference the authors report as statistically significant with P equal to 0.035. In this cohort, ipsilateral cervical lymph node metastases were more frequent among 18F-FAPI-positive thyroid lesions than among tracer-negative lesions (60% vs. 20%, P = 0.035).

Two quantitative parameters stood out in the analysis. The LNM-positive group showed higher FTV, defined as FAP expression tumor volume, with a P value of 0.004, and higher TLF, or total lesion FAP expression, with a P value of 0.044. FTV was defined as FAP expression tumor volume and TLF as total lesion FAP expression; both were higher in the LNM-positive group.

The correlations extended to the number of metastatic nodes as well. Lymph node count correlated positively with FTV at a correlation coefficient of 0.474 with P equal to 0.004, and with TLF at 0.398 with P equal to 0.018. LNM number correlated positively with FTV (r = 0.474, P = 0.004) and TLF (r = 0.398, P = 0.018), an association the authors cite in support of the supplementary value of [18F]-FAPI PET/CT for preoperative staging and risk stratification in differentiated thyroid cancer.

Taken together, the authors conclude that 18F-FAPI PET/CT offers diagnostic accuracy comparable to ultrasound for primary thyroid lesions while providing superior pathological consistency for detecting cervical lymph node metastases, and that tracer-positive primaries carry a higher risk of ipsilateral nodal spread. They frame these results as supporting a supplementary role for the technique in preoperative staging and risk stratification of differentiated thyroid cancer, complementing rather than replacing existing imaging. Because the study was prospective and pathology-confirmed, the agreement measures rest on direct tissue verification rather than clinical follow-up alone.

Several caveats temper the strength of these conclusions. The cohort comprised 43 participants with 58 lesions, a modest sample size that limits the precision of the reported kappa values, percentages and correlation coefficients, and the findings will need confirmation in larger and more diverse populations before practice changes. The study also focused specifically on papillary thyroid carcinoma, the most common histological subtype, so extrapolation to other thyroid cancer types remains untested. The authors conclude that [18F]-FAPI PET/CT showed diagnostic accuracy comparable to ultrasound for primary thyroid lesions, superior pathological consistency for detecting cervical lymph node metastases, and a higher risk of ipsilateral cervical LNM among tracer-positive lesions, supporting its supplementary value for preoperative staging and risk stratification in differentiated thyroid cancer.

Subject of Research: Preoperative 18F-FAPI PET/CT for detecting papillary thyroid carcinoma and cervical lymph node metastases

Article Title: Diagnostic value of preoperative 18F-FAPI PET/CT in primary papillary thyroid carcinoma and cervical lymph node metastases: a prospective study

Article References: Wang, Y., Qiao, F., Zhang, L., Zhai, L., Liu, Y., Li, N., Xu, K., & Zhang, W. (2026). Diagnostic value of preoperative 18F-FAPI PET/CT in primary papillary thyroid carcinoma and cervical lymph node metastases: a prospective study. EJNMMI Research. https://doi.org/10.1186/s13550-026-01507-8

Image Credits: AI Generated

DOI: 10.1186/s13550-026-01507-8

Keywords: 18F-FAPI, PET/CT, papillary thyroid carcinoma, cervical lymph node metastases, ultrasound, differentiated thyroid cancer, preoperative staging, FAP expression, risk stratification, nuclear medicine, thyroid nodules, FTV