Abstract
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Objectives To synthesize a novel albumin-binding PET radiotracer 68Ga-NEB, validate its pharmacokinetics, safety, dosimetry, and document the first-in-human application.
Methods A cyclic chelator, 1,4,7-triazacyclononane-N,N’,N”-triacetic acid (NOTA) conjugated truncated form of Evans blue (NEB) was synthesized and labeled with 68Ga. Sixty-minute dynamic PET imaging and biodistribution in normal mice were performed to evaluate the in vivo pharmacokinetics. After a clinical trial was approved by the institute review board, three healthy volunteers were enrolled to validate the safety of 68Ga-NEB and a total of 8 patients with written informed consent were recruited. The diagnosis was based on pathological result of surgical removal or biopsy.
Results The whole labeling process of 68Ga-NEB took about 30 min with a radiochemical purity of greater than 95%. After intravenous injection, 68Ga-NEB forms complex with serum albumin and majority of the radioactivity was retained in the blood circulation. With an injected dose of 3-4 mCi (121-148 MBq), a patient would be exposed to a radiation dose of 2.65 mSv, which is much lower than the dose limit as set by the FDA. The tracer was demonstrated to be safe in both healthy volunteers and patients without side effects or allergies. The small scale clinical study substantiated the role of NEB as a blood pool imaging agent in delineating vascular anomalies including abdominal aortic aneurysm (AAA) and arteriovenous malformation (AVM), mapping of sentinel lymph nodes (SNLs) and evaluation of blood supply to brain tumors.
Conclusions Easy labeling with different positron emitters of various half-lives, excellent pharmacokinetics and imaging quality warrant further clinical applications of NEB derived PET tracers for blood pool, vascular permeability and lymphatic imaging.
Research Support IRP of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH)