First-in-human Evaluation of Safety and Dosimetry of [Cu]FBP8: A fibrin-binding PET Probe.

Purpose: This study presents for the first time in humans the biodistribution, clearance and dosimetry estimates of [Cu]Fibrin Binding Probe #8 ([Cu]FBP8) in healthy subjects. [Cu]FBP8-PET previously demonstrated its potential in two recent applications: thrombus imaging and pulmonary fibrosis.

Procedures: This prospective study included 8 healthy subjects to evaluate biodistribution, safety and dosimetry estimates of [Cu]FBP8, a fibrin-binding positron emission tomography (PET) probe. All subjects underwent up to 3 sessions of PET/Magnetic Resonance Imaging (PET/MRI) 0-2 h, 4 h and 24 h post injection. Dosimetry estimates were obtained using OLINDA 2.2 software.

Results: Subjects were injected with 400 MBq of [Cu]FBP8. Subjects did not experience adverse effects due to the injection of the probe. [Cu]FBP8 PET images demonstrated fast blood clearance (half-life = 67 min) and renal excretion of the probe, showing low background signal across the body. The organs with the higher doses were: the urinary bladder (0.075 vs. 0.091 mGy/MBq for males and females, respectively); the kidneys (0.050 vs. 0.056 mGy/MBq respectively); and the liver (0.027 vs. 0.035 mGy/MBq respectively). The combined mean effective dose for males and females was 0.016 ± 0.0029 mSv/MBq, lower than the widely used [F]fluorodeoxyglucose ([F]FDG, 0.020mSv/MBq).

Conclusions: This study demonstrates the following properties of the [Cu]FBP8 probe: low dosimetry estimates; fast blood clearance and renal excretion; low background signal; and whole-body acquisition within 20 min in a single session. These properties provide the basis for [Cu]FBP8 to be an excellent candidate for whole-body non-invasive imaging of fibrin, an important driver/feature in many cardiovascular, oncological and neurological conditions.