RT Journal Article SR Electronic T1 18F-ML-10, a PET Tracer for Apoptosis: First Human Study JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 720 OP 725 DO 10.2967/jnumed.110.081786 VO 52 IS 5 A1 Höglund, Johanna A1 Shirvan, Anat A1 Antoni, Gunnar A1 Gustavsson, Sven-Åke A1 Långström, Bengt A1 Ringheim, Anna A1 Sörensen, Jens A1 Ben-Ami, Miri A1 Ziv, Ilan YR 2011 UL http://jnm.snmjournals.org/content/52/5/720.abstract AB 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.