18F-ML-10, a PET Tracer for Apoptosis: First Human Study

Journal of Nuclear Medicine

Anna Ringheim¹  Gunnar Antoni¹  Miri Ben-Ami¹  Anat Shirvan¹  Sven-Åke Gustavsson¹  Jens Sörensen¹  Johanna Höglund¹  Ilan Ziv¹  Bengt Långström¹ 

关键词: molecular imaging;    apoptosis;    PET;    dosimetry;    biodistribution;   

DOI  :  10.2967/jnumed.110.081786

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Clinical PET of apoptosis may have substantial value in advancing patient care. We report here the first-in-humans study with 18F-labeled 2-(5-fluoropentyl)-2-methyl malonic acid (18F-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. Methods: 18F-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. Results: 18F-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 18F-ML-10 was safe, without adverse effects. Conclusion: 18F-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.

【 授权许可】

Unknown