Hou Lu, Wang Yanjuan, Fu Haitian, Chen Liping, Yu Chunjing, Chen Xiaoyuan, Zhang Jingjing
Department of Nuclear Medicine, Affiliated Hospital of Jiangnan University, No. 1000, Hefeng Road, Wuxi, Jiangsu, 214000, China.
Wuxi School of Medicine, Jiangnan University, Wuxi, China.
Eur J Nucl Med Mol Imaging. 2025 Apr 10. doi: 10.1007/s00259-025-07245-8.
Preclinical studies have shown that the long-acting PSMA-targeting radiopharmaceutical [Lu]Lu-LNC1011 based on dansylated amino acid modification had high tumor uptake and prolonged retention. This study aimed to explore its safety and efficacy in patients with metastatic castration-resistant prostate cancer (mCRPC).
Eight mCRPC patients who met the inclusion criteria received intravenous treatment with [Lu]Lu-LNC1011. Treatment was repeated every 6 weeks for up to a maximum of 6 cycles. Molecular imaging and hematology markers were the main evaluation indicators. The primary endpoints were biochemical (PSA) response and molecular imaging response. Toxicity grading was assessed using the Common Terminology Criteria for Adverse Events version 5.0.
Hematological toxicity was the primary side effect. In all patients, adverse events (AEs) after [Lu]Lu-LNC1011 treatment were primarily characterized by decreased levels of hemoglobin, white blood cells and platelets. Grade 3 anemia was recorded in 1 patient, and grade 2 leukopenia and thrombocytopenia were recorded in 4 patients. The average systemic effective dose was 0.18 mSv/MBq, and the kidney was the organ with the highest absorbed dose (3.11 ± 0.26 mSv/MBq). Long half-life (71.30 ± 8.23 h) and high absorbed dose [5.77, (range 5.5-14 Gy/GBq)] were calculated in the lesions. All patients had a more than 50% decline of PSA during treatment, and one patient dropped to 0 ng/mL. According to assessment criteria adapted from the PERCIST v.1.0 criteria, complete response, partial response, and disease progression were observed in 2 (25%), 4 (50%), and 2 (25%) patients, respectively.
[Lu]Lu-LNC1011 was well tolerated and had acceptable side effects for PSMA-targeted radioligand therapy. Tumor lesions received high radiation doses and had excellent responses to the treatment. Dose escalation studies in a larger number of patients are worth pursuing and necessary to confirm these results. URL OF REGISTRY: https://clinicaltrials.gov/study/NCT06809426?term=NCT06809 .
NCT06809426, registration date: 2025-01-23.
临床前研究表明，基于丹磺酰化氨基酸修饰的长效靶向前列腺特异性膜抗原（PSMA）的放射性药物[镥]镥-LNC1011具有高肿瘤摄取率和延长的滞留时间。本研究旨在探讨其在转移性去势抵抗性前列腺癌（mCRPC）患者中的安全性和疗效。
8例符合纳入标准的mCRPC患者接受了[镥]镥-LNC1011静脉注射治疗。每6周重复治疗，最多进行6个周期。分子影像学和血液学指标为主要评估指标。主要终点为生化（前列腺特异性抗原，PSA）反应和分子影像学反应。使用不良事件通用术语标准第5.0版进行毒性分级评估。
血液学毒性是主要副作用。在所有患者中，[镥]镥-LNC1011治疗后的不良事件主要表现为血红蛋白、白细胞和血小板水平降低。1例患者出现3级贫血，4例患者出现2级白细胞减少和血小板减少。平均全身有效剂量为0.18 mSv/MBq，肾脏是吸收剂量最高的器官（3.11±0.26 mSv/MBq）。病灶的半衰期长（71.30±8.23小时）且吸收剂量高[5.77，（范围5.5 - 14 Gy/GBq）]。所有患者在治疗期间PSA下降超过50%，1例患者降至0 ng/mL。根据改编自实体瘤疗效评价标准（PERCIST）v.1.0标准的评估标准，分别有2例（25%）、4例（50%）和2例（25%）患者观察到完全缓解、部分缓解和疾病进展。
[镥]镥-LNC1011耐受性良好，对于靶向PSMA的放射性配体治疗具有可接受的副作用。肿瘤病灶接受了高辐射剂量且对治疗有良好反应。有必要开展更多患者的剂量递增研究以证实这些结果。注册网址：https://clinicaltrials.gov/study/NCT06809426?term=NCT06809 。
NCT06809426，注册日期：2025年1月23日。
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