Uppsala Imanet AB, GE Healthcare, Uppsala, Sweden.
J Nucl Med. 2011 May;52(5):720-5. doi: 10.2967/jnumed.110.081786. Epub 2011 Apr 15.
Clinical PET of apoptosis may have substantial value in advancing patient care. We report here the first-in-humans study with (18)F-labeled 2-(5-fluoropentyl)-2-methyl malonic acid ((18)F-ML-10), a small-molecule PET tracer for apoptosis. Presented are the dosimetry, biodistribution, stability, and safety profiles of this PET tracer in healthy human volunteers. Also reported is tracer binding to targeted apoptotic cells in testicular tissue, where a relative abundance of apoptotic cells is normally observed.
(18)F-ML-10 (233 ± 90 MBq) was intravenously administered to 8 healthy subjects, followed by whole-body PET/CT for 220 min. Serial blood and urine samples were collected for radioactivity measurement, and plasma tracer stability was assessed by high-performance liquid chromatography. Dosimetry calculations were performed using OLINDA/EXM software.
(18)F-ML-10 manifested high stability in vivo and rapid distribution followed by fast clearance, with an elimination half-life of 1.3 ± 0.1 and 1.1 ± 0.2 h from the blood and from all other organs, respectively, and excretion through the urine. Dosimetry showed an average effective whole-body dose of 15.4 ± 3.7 μSv/MBq, with the urinary bladder being the dose-limiting organ. Selective accumulation and retention of the tracer in the testes was observed in all male subjects, a finding also demonstrated in mice using both small-animal PET and histopathology, confirming binding to apoptotic cells. Administration of (18)F-ML-10 was safe, without adverse effects.
(18)F-ML-10 administered to healthy humans demonstrated a favorable dosimetry, biodistribution, stability, and safety profile. Binding to apoptotic sites was also demonstrated. These data support further development of this small-molecule probe for clinical PET of apoptosis.
临床 PET 细胞凋亡可能在提高患者护理方面具有重要价值。我们在此报告首例人体研究，研究内容为使用放射性核素标记的 2-（5-氟戊基）-2-甲基丙二酸（（18）F-ML-10），这是一种用于细胞凋亡的小分子 PET 示踪剂。本研究报告了这种新型 PET 示踪剂在健康志愿者中的剂量学、生物分布、稳定性和安全性概况。同时还报告了示踪剂在睾丸组织中靶向凋亡细胞的结合情况，因为睾丸组织中通常存在大量凋亡细胞。
8 位健康志愿者静脉注射（18）F-ML-10（233 ± 90 MBq），随后进行 220 分钟的全身 PET/CT 扫描。采集血样和尿样以测量放射性，通过高效液相色谱法评估血浆示踪剂的稳定性。使用 OLINDA/EXM 软件进行剂量计算。
（18）F-ML-10 体内稳定性高，分布迅速，清除迅速，血液和其他所有器官的消除半衰期分别为 1.3 ± 0.1 和 1.1 ± 0.2 小时，通过尿液排泄。剂量学显示，平均有效全身剂量为 15.4 ± 3.7 μSv/MBq，膀胱是剂量限制器官。所有男性志愿者的睾丸均可见示踪剂选择性聚集和保留，在使用小动物 PET 和组织病理学的小鼠模型中也观察到了这种情况，证实了与凋亡细胞的结合。（18）F-ML-10 给药安全，无不良反应。
（18）F-ML-10 对健康人进行给药，显示出良好的剂量学、生物分布、稳定性和安全性概况。还证明了与凋亡部位的结合。这些数据支持进一步开发这种小分子探针用于细胞凋亡的临床 PET。
