每年诊断出的 50 万甲状腺癌病例中，95% 是分化型甲状腺癌。尽管临床指南建议手术切除后进行放射性碘消融，但钠碘同向转运体表达的丧失会导致高达 20% 的分化型甲状腺癌变得放射性碘难治性。对于放射性碘难治性疾病患者，迫切需要新的诊断和治疗方法。我们评估了促甲状腺激素受体作为分化型甲状腺癌成像的潜在靶点。我们对包含 52 个 Hurthle 细胞癌的组织微阵列进行了免疫染色，以确认促甲状腺激素受体的表达。我们将放射性标记的螯合剂去铁胺与重组人促甲状腺激素类似物超级激动剂 TR1402 与 89Zr 缀合（t1/2 = 78.4 h，β = 22.7%），生成 [89Zr]Zr-TR1402。我们对表达高促甲状腺激素受体和低促甲状腺激素受体的 THJ529T 和 FTC133 甲状腺癌细胞系进行了体外摄取测定。我们在携带促甲状腺激素受体阳性 THJ529T 肿瘤的雄性无胸腺裸鼠中进行了体内正电子发射断层扫描/计算机断层扫描和生物分布研究。免疫组织化学分析显示，62% 的患者（27 例原发性和 5 例复发性）为促甲状腺激素受体膜性肿瘤免疫染色阳性。促甲状腺激素受体阳性 THJ529T 甲状腺癌细胞系中 1nM [89Zr]Zr-TR1402 的体外摄取为 38 ± 17% 结合/毫克，而低表达细胞系中为 3.2 ± 0.5 (P < .01) ，在 FTC133 细胞系中也观察到类似的差异 (P < .0001)。体内和生物分布研究表明，[89Zr]Zr-TR1402 在表达甲状腺刺激激素受体的肿瘤中被吸收，注射后 3 天的平均注射剂量/克百分比为 1.9 ± 0.4。我们对甲状腺刺激激素的观察组织微阵列中的激素受体表达以及促甲状腺激素受体阳性甲状腺癌细胞和肿瘤中的 [89Zr]Zr-TR1402 积累表明促甲状腺激素受体是分化型甲状腺癌成像的一个有前景的靶点。版权所有 © 2023 Elsevier Inc.版权所有。

Of the half a million cases of thyroid cancer diagnosed annually, 95% are differentiated thyroid cancers. Although clinical guidelines recommend surgical resection followed by radioactive iodine ablation, loss of sodium-iodine symporter expression causes up to 20% of differentiated thyroid cancers to become radioactive iodine refractory. For patients with radioactive iodine refractory disease, there is an urgent need for new diagnostic and therapeutic approaches. We evaluated the thyroid-stimulating hormone receptor as a potential target for imaging of differentiated thyroid cancer.We immunostained tissue microarrays containing 52 Hurthle cell carcinomas to confirm thyroid-stimulating hormone receptor expression. We radiolabeled chelator deferoxamine conjugated to recombinant human thyroid-stimulating hormone analog superagonist TR1402 with 89Zr (t1/2 = 78.4 h, β+ =22.7%) to produce [89Zr]Zr-TR1402. We performed in vitro uptake assays in high-thyroid-stimulating hormone receptor and low-thyroid-stimulating hormone receptor-expressing THJ529T and FTC133 thyroid cancer cell lines. We performed in vivo positron emission tomography/computed tomography and biodistribution studies in male athymic nude mice bearing thyroid-stimulating hormone receptor-positive THJ529T tumors.Immunohistochemical analysis revealed 62% of patients (27 primary and 5 recurrent) were thyroid-stimulating hormone receptor membranous immunostain positive. In vitro uptake of 1nM [89Zr]Zr-TR1402 was 38 ± 17% bound/mg in thyroid-stimulating hormone receptor-positive THJ529T thyroid cancer cell lines compared to 3.2 ± 0.5 in the low-expressing cell line (P < .01), with a similar difference seen in FTC133 cell lines (P < .0001). In vivo and biodistribution studies showed uptake of [89Zr]Zr-TR1402 in thyroid-stimulating hormone receptor-expressing tumors, with a mean percentage of injected dose/g of 1.9 ± 0.4 at 3 days post-injection.Our observation of thyroid-stimulating hormone receptor expression in tissue microarrays and [89Zr]Zr-TR1402 accumulation in thyroid-stimulating hormone receptor-positive thyroid cancer cells and tumors suggests thyroid-stimulating hormone receptor is a promising target for imaging of differentiated thyroid cancer.Copyright © 2023 Elsevier Inc. All rights reserved.