基于生长抑素受体表达的转移性乳腺癌的奥曲肽 PET/CT 与 Ac-Dotatate 治疗
Dotatate PET/CT and Ac-Dotatate Therapy for Somatostatin Receptor-expressing Metastatic Breast Cancer.
机构信息
From the Department of Molecular Imaging and Therapy, Hoag Family Cancer Institute, 16105 Sand Canyon Ave, Irvine, CA 92618 (G.A.U.); Department of Radiology and Translational Genomics (G.A.U.) and Department of Medicine (L.A.V.), University of Southern California, Los Angeles, Calif; and RayzeBio, San Diego, CA (G.L., D.F.).
出版信息
Radiology. 2024 Jul;312(1):e233408. doi: 10.1148/radiol.233408.
Background Somatostatin receptors, and specifically somatostatin receptor type 2 (SSTR2), have primarily been associated with neuroendocrine tumors and have revolutionized the imaging and therapy of patients with these tumors. SSTR2 is expressed on other tumors at lower prevalence. Purpose To evaluate the potential of SSTR2-targeted imaging and therapy in patients with breast cancer. Materials and Methods In a preclinical experiment, SSTR2 expression was assessed in tissue microarrays of breast cancer samples using H-score analysis. H-scores higher than 50 (0-300 scale) were considered positive. Then, a prospective phase 2 clinical trial of SSTR2-targeted tetraazacyclododecane tetraacetic acid octreotate (Dotatate) PET/CT was performed in participants with biopsy-proven estrogen receptor (ER)-positive breast cancer from January to August 2023. A positive Dotatate PET/CT scan was defined as tumors with a Krenning score of 3 (avidity greater than liver) or 4 (avidity greater than spleen). The proportion of positive scans and the 95% CI were calculated. One participant with metastatic ER-positive breast cancer and a Krenning 4 Dotatate PET/CT result underwent treatment with SSTR2-targeted actinium 225 (Ac) Dotatate. Results Preclinical microarrays demonstrated that 63 of 123 ER-positive breast cancer tissue samples (51% [95% CI: 42, 60]) but only 22 of 121 ER-negative breast cancer tissue samples (18% [95% CI: 12, 26]) were enriched for SSTR2 ( < .001). Thirty female participants (mean age, 66 years ± 15) with metastatic ER-positive breast cancer were accrued to the phase 2 SSTR2-targeted imaging trial and underwent Dotatate PET/CT. Dotatate PET/CT demonstrated that nine of 30 participants (30% [95% CI: 15, 49]) had tumors with Krenning scores of 3 or 4, indicating strong SSTR2 expression. SSTR2-targeted therapy with alpha-emitting Ac-Dotatate resulted in a near complete response in a heavily pretreated participant with metastatic ER-positive breast cancer and a Krenning 4 Dotatate PET result. Conclusion Molecular imaging targeting SSTR2 and radioligand therapy with SSTR2-targeted Ac-Dotatate enables a new therapeutic option for patients with metastatic breast cancer. Clinical trial registration no. NCT05880394 © RSNA, 2024 See also the editorial by Lin and Choyke in this issue.
背景 生长抑素受体，特别是生长抑素受体 2（SSTR2），主要与神经内分泌肿瘤相关，并彻底改变了这些肿瘤患者的影像学和治疗方法。SSTR2 在其他肿瘤中的表达率较低。目的 评估 SSTR2 靶向成像和治疗在乳腺癌患者中的潜力。材料与方法 在一项临床前实验中，使用 H 评分分析评估了乳腺癌样本组织微阵列中的 SSTR2 表达。H 评分高于 50（0-300 范围）被认为是阳性。然后，在 2023 年 1 月至 8 月期间，对经活检证实的雌激素受体（ER）阳性乳腺癌患者进行了 SSTR2 靶向四氮杂环十二烷四乙酸奥曲肽（Dotatate）PET/CT 的前瞻性 2 期临床试验。阳性 Dotatate PET/CT 扫描定义为肿瘤的 Krenning 评分≥3（比肝脏摄取更多）或≥4（比脾脏摄取更多）。计算阳性扫描的比例和 95%CI。一名患有转移性 ER 阳性乳腺癌且 Krenning 评分 4 的 Dotatate PET/CT 结果阳性的患者接受了 SSTR2 靶向锕 225（Ac）Dotatate 治疗。结果 临床前微阵列显示，123 例 ER 阳性乳腺癌组织样本中有 63 例（51%[95%CI：42，60]）但 121 例 ER 阴性乳腺癌组织样本中只有 22 例（18%[95%CI：12，26]）富含 SSTR2（<.001）。30 名患有转移性 ER 阳性乳腺癌的女性参与者（平均年龄 66 岁±15 岁）入组了 2 期 SSTR2 靶向成像试验，并接受了 Dotatate PET/CT 检查。Dotatate PET/CT 显示，30 名参与者中有 9 名（30%[95%CI：15，49]）的肿瘤 Krenning 评分≥3 或 4，表明 SSTR2 表达强烈。接受 SSTR2 靶向α发射性 Ac-Dotatate 治疗的一位患有转移性 ER 阳性乳腺癌且 Krenning 评分 4 的 Dotatate PET 结果阳性的患者获得了近乎完全缓解。结论 靶向 SSTR2 的分子成像和 SSTR2 靶向放射性配体疗法 Ac-Dotatate 为转移性乳腺癌患者提供了新的治疗选择。临床试验注册号 NCT05880394 © RSNA，2024 也请参见本期 Lin 和 Choyke 的社论。
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