Background: Lung metastasis from differentiated thyroid cancer (DTC) in children and young adults (CAYA) is estimated at 25%, which is 3–4 times higher than in adults. Lung metastases may respond to radioactive iodine (RAI) therapy and overall survival is excellent. Associations with lung metastasis include lateral lymph node (LN) disease although CAYA data are limited. We investigated factors associated with lung metastasis in children and adolescents and described their presentation and outcome. Methods: A retrospective review of medical records from 1998 to 2017 in patients aged <18 years treated at a tertiary pediatric center was carried out. Data on age, clinical features at diagnosis, histology, biochemistry, imaging, RAI therapy, and outcome were collected. Results: Patients treated for DTC totaled 98 and 19 of 98 (19%) patients had lung metastasis; 17 of 19 (89%) patients were identified within 6 months from thyroidectomy. Patients with lung metastasis were younger ( p < 0.001)—40% <13 years old had lung metastasis—and had a larger primary tumor diameter ( p = 0.01). Absence of LN disease had negative predictive values ≥90% ( p < 0.02). Patients with lung metastasis had a higher postoperative thyrotropin-stimulated thyroglobulin (Tg) ( p < 0.001), ≥2 ng/mL in 10 of 11 (91%) patients, and 100% had an elevated preoperative Tg (>60 ng/mL). Post-therapy whole body scan (WBS) identified most metastasis (13 of 17 patients), which were mostly diffuse (11 of 19 patients). Discordant findings were found between WBS and computed tomography (CT) at diagnosis (2 patients), WBS and CT during surveillance (3 patients), and diagnostic and post-therapy WBS (2 patients). Final outcome was “excellent” in 3 of 19 (16%) patients, “biochemically persistent” in 1 of 19 (5%) patients, “structurally persistent” in 13 of 19 (68%) patients—including 1 death—and indeterminate in 2 of 19 (11%) patients. Postoperative Tg correlated with response to therapy. Lung metastasis pattern and RAI cumulative activity were not predictive of response to therapy. Conclusions: Lung metastases are mostly observed at diagnosis of DTC and higher suspicion should be maintained in CAYA who are younger, have LN disease, and have elevated postoperative Tg. Preoperative Tg shows promise as another predictive marker, but limited sample size precludes generalization. “Excellent” response to therapy is uncommon—multiple RAI courses do not necessarily improve outcome—response appears unrelated to RAI activity or metastasis pattern.

A 52-year-old woman with metastatic pancreatic adenocarcinoma underwent imaging with ¹⁸F-FDG PET/CT and ⁶⁸Ga-FAPI-46 PET/CT, which demonstrated malignancy recurrence in the surgical bed with multiple metastatic lesions, more extensive on ⁶⁸Ga-FAPI-46 PET/CT. The patient was a candidate for therapy with ¹⁷⁷Lu-FAPI-46 due to high uptake of lesions in ⁶⁸Ga-FAPI-46 images and no other available therapeutic option. Posttreatment ¹⁷⁷Lu-FAPI-46 scans showed rather rapid washout of the radiopharmaceutical from tumoral lesions. This case report suggests that, although ⁶⁸Ga-FAPI-46 is a promising agent for tumor imaging, ¹⁷⁷Lu-FAPI-46 may not be an optimal compound for theranostic applications.

Peptide-receptor imaging and therapy with radiolabeled somatostatin analogs such as ⁶⁸Ga-DOTA-TATE and ¹⁷⁷Lu-DOTA-TATE have become an effective treatment option for SSTR-positive neuroendocrine tumors. The purpose of this study was to evaluate the correlation of somatostatin receptor-2 (SSTR2) expression with ⁶⁸Ga-DOTA-TATE uptake and ¹⁷⁷Lu-DOTA-TATE therapy in neuroblastoma (NB) xenograft models. We demonstrated variable SSTR2 expression profiles in eight NB cell lines. From micro-PET imaging and autoradiography, a higher uptake of ⁶⁸Ga-DOTA-TATE was observed in SSTR2 high-expressing NB xenografts (CHLA-15) compared to SSTR2 low-expressing NB xenografts (SK-N-BE(2)). Combined autoradiography-immunohistochemistry revealed histological colocalization of SSTR2 and ⁶⁸Ga-DOTA-TATE uptake in CHLA-15 tumors. With a low dose of ¹⁷⁷Lu-DOTA-TATE (20 MBq/animal), tumor growth inhibition was achieved in the CHLA-15 high SSTR2 expressing xenograft model. Although, in vitro, NB cells showed variable expression levels of norepinephrine transporter (NET), a molecular target for ¹³¹I-MIBG therapy, low ¹²³I-MIBG uptake was observed in all selected NB xenografts. In conclusion, SSTR2 expression levels are associated with ⁶⁸Ga-DOTA-TATE uptake and antitumor efficacy of ¹⁷⁷Lu-DOTA-TATE. ⁶⁸Ga-DOTA-TATE PET is superior to ¹²³I-MIBG SPECT imaging in detecting NB tumors in our model. Radiolabeled DOTA-TATE can be used as an agent for NB tumor imaging to potentially discriminate tumors eligible for ¹⁷⁷Lu-DOTA-TATE therapy.