18F-ML-10, a PET tracer for apoptosis: first XXXX study.

@entity1 @entity8984 @entity19 @entity72813
Clinical PET of apoptosis may have substantial value in advancing @entity1 care. We report here the first-in- @entity1 study with @entity8984 -labeled @entity72813 ( @entity8984 -ML-10), a small-molecule PET tracer for apoptosis. Presented are the dosimetry, biodistribution, stability, and safety profiles of this PET tracer in healthy @entity1 volunteers. Also reported is tracer binding to targeted apoptotic cells in testicular tissue, where a relative abundance of apoptotic cells is normally observed. METHODS: @entity8984 -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: @entity8984 -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  Sv/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 @entity19 using both small-animal PET and histopathology, confirming binding to apoptotic cells. Administration of @entity8984 -ML-10 was safe, without adverse effects. CONCLUSION: @entity8984 -ML-10 administered to healthy @entity1 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.
