This image is the first reported instance of medullary thyroid carcinoma (MTC), in which [68Ga]Ga-DOTA-FAPI-04 provided a more accurate assessment of the disease’s metastatic spread than [68Ga]Ga-DOTATOC. A 40-year-old male patient initially presented with a thyroid lesion along with several cervical and thoracic lymph nodes enlargement on CT scan. Additionally, there were sternal bone and liver lesions suggestive of metastases. A left cervical lymph node biopsy confirmed the presence of MTC. The patient received nine cycles of chemotherapy, which only exerted limited local partial control. A follow-up CT scan showed metastatic disease progression. [68Ga]Ga-DOTATOC scan was requested and showed only mild expression of somatostatin receptors in the thyroid and nearby lymph nodes (a–d, arrows). However, there was no significant expression detected in the bones or the liver (a–d, arrow heads). Therefore, this case was not considered a potential candidate for [177Lu]Lu-DOTATATE therapy. In parallel, [68Ga]Ga-DOTA-FAPI-04 was ordered to better evaluate the extent of the disease, which revealed an additional picture of progressive metastatic disease involving the liver, sternum, and iliac bones (e–h, arrows). In addition to the observed discordance (i), biochemical progression was also evident, demonstrating markedly elevated tumor markers (j). Recent studies have shown moderate uptake of the [68Ga]Ga-DOTA-FAPI-04 in MTC [1, 2]. Progressive metastatic MTC usually has limited treatment options [3], a worse prognosis [4], and higher mortality rates [5]. MTC undergoes a progression in which initially well-differentiated lesions express somatostatin receptors (SSTR), but later transition to an undifferentiated state with poor SSTR expression [6]. This shift is accompanied by a significant rise in carcinoembryonic antigen (CEA) tumor marker, which is more useful for serial monitoring of undifferentiated cases than thyrocalcitonin [6]. In these circumstances, molecular imaging with [18F]fluorodeoxyglucose can aid in determining the extent of the disease [7]. This observed discrepancy supports the potential efficacy of [68Ga]Ga-DOTA-FAPI-04 in the management of MTC. The added value of [68Ga]Ga-DOTA-FAPI-04 lies in its potential to provide more accurate staging of multiple cancers and the potential use of fibroblast activation protein inhibitor (FAPI) in radioligand theranostics approach [8, 9]. However, the significance of such evidence is limited as it only represents one case. Therefore, further studies are still needed to approve its implications for both diagnostic and therapeutic purposes.

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