First-in-human Evaluation of Safety and Dosimetry of [64Cu]FBP8: A fibrin-binding PET Probe

• Published in: Molecular imaging and biology Vol. 27; no. 1; pp. 99 - 108
• Main Authors: Izquierdo-Garcia, David, Désogère, Pauline, Philip, Anne L., Sosnovik, David E., Catana, Ciprian, Caravan, Peter
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.02.2025; Springer Nature B.V
• Subjects: Adult; Binding; Biodistribution; Blood; Copper Radioisotopes - chemistry; Copper Radioisotopes - pharmacokinetics; Dosimeters; Dosimetry; Estimates; Excretion; Female; Females; Fibrin; Fibrin - metabolism; Fibrosis; Fluorine isotopes; Humans; Imaging; Injection; Lung diseases; Magnetic Resonance Imaging; Male; Males; Medical imaging; Medicine; Medicine & Public Health; Middle Aged; Positron emission; Positron emission tomography; Positron-Emission Tomography - methods; Prospective Studies; Radiology; Radiometry; Renal function; Research Article; Thrombosis; Tissue Distribution; Urinary bladder; Young Adult; Fibrin; Positron emission tomography (PET); PET/MRI; Magnetic resonance imaging (MRI); Dosimetry; Effective dose; Probe; Biodistribution; Blood clots
• ISSN: 1536-1632; 1860-2002
• DOI: 10.1007/s11307-024-01973-3

Purpose This study presents for the first time in humans the biodistribution, clearance and dosimetry estimates of [ 64 Cu]Fibrin Binding Probe #8 ([ 64 Cu]FBP8) in healthy subjects. [ 64 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 [ 64 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 [ 64 Cu]FBP8. Subjects did not experience adverse effects due to the injection of the probe. [ 64 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 [ 18 F]fluorodeoxyglucose ([ 18 F]FDG, 0.020mSv/MBq). Conclusions This study demonstrates the following properties of the [ 64 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 [ 64 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.