Clinical Translation of an Albumin-Binding PET Radiotracer 68Ga-NEB.
الكلمات الدالة
نبذة مختصرة
Suitably labeled Evans blue dye has been successfully applied to evaluate cardiac function, vascular permeability, and lymphatic imaging in preclinical settings. This study documented the first-in-human application of 68Ga-1,4,7-triazacyclononane-N,N',N″-triacetic acid (NOTA)-NEB.
METHODS
The NOTA-conjugated truncated form of Evans blue, NEB, was labeled with 68Ga and tested in BALB/C mice for dynamic PET and ex vivo biodistribution studies. Three healthy volunteers (2 men and 1 woman) underwent 90-min whole-body dynamic PET. The absorbed doses for major organs and whole body were calculated using OLINDA/EXM software. Eleven patients with focal hepatic lesions diagnosed by enhanced CT or MR imaging were subjected to whole-body PET/CT acquisitions at 30 min after intravenous injection of 111-148 MBq (3-4 mCi) of 68Ga-NEB.
RESULTS
NEB dye was labeled with 68Ga (half-time, 68 min) with high yield and purity. After intravenous injection, 68Ga-NEB formed a complex with serum albumin, thus most of the radioactivity was retained in blood circulation. The tracer was demonstrated to be safe in both healthy volunteers and recruited patients without side effects or allergies. Among the 11 patients, hemangiomas showed much higher 68Ga-NEB signal intensity than the surrounding normal hepatic tissues, whereas no apparent difference between lesions and hepatic tissues was identified on 18F-FDG PET. All other focal hepatic lesions including hepatocellular carcinoma, hepatic cysts, and neuroendocrine tumor liver metastases showed negative 68Ga-NEB contrast to hepatic tissues.
CONCLUSIONS
As a blood-pool imaging agent, 68Ga-NEB is safe to use in the clinic, and our preliminary studies demonstrate the value of differentiating hepatic hemangioma from other benign or malignant focal hepatic lesions. Easy labeling with different positron emitters of various half-lives, excellent pharmacokinetics, and imaging quality warrant further clinical applications of NEB-based PET tracers.
