RESUMEN
PURPOSE: A reliable and routine process to introduce a new ¹8F-labeled dimeric RGD-peptide tracer ([¹8F]FPP(RGD2) for noninvasive imaging of α(v)ß3 expression in tumors needed to be developed so the tracer could be evaluated for the first time in man. Clinical-grade [¹8F]FPP(RGD)2 was screened in mouse prior to our first pilot study in human. PROCEDURES: [¹8F]FPP(RGD)2 was synthesized by coupling 4-nitrophenyl-2-[¹8F]fluoropropionate ([¹8F]NPE) with the dimeric RGD-peptide (PEG3-c(RGDyK)2). Imaging studies with [¹8F]FPP(RGD)2 in normal mice and a healthy human volunteer were carried out using small animal and clinical PET scanners, respectively. RESULTS: Through optimization of each radiosynthetic step, [¹8F]FPP(RGD)2 was obtained with RCYs of 16.9 ± 2.7% (n = 8, EOB) and specific radioactivity of 114 ± 72 GBq/µmol (3.08 ± 1.95 Ci/µmol; n = 8, EOB) after 170 min of radiosynthesis. In our mouse studies, high radioactivity uptake was only observed in the kidneys and bladder with the clinical-grade tracer. Favorable [¹8F]FPP(RGD)2 biodistribution in human studies, with low background signal in the head, neck, and thorax, showed the potential applications of this RGD-peptide tracer for detecting and monitoring tumor growth and metastasis. CONCLUSIONS: A reliable, routine, and automated radiosynthesis of clinical-grade [¹8F]FPP(RGD)2 was established. PET imaging in a healthy human volunteer illustrates that [¹8F]FPP(RGD)2 possesses desirable pharmacokinetic properties for clinical noninvasive imaging of α(v)ß3 expression. Further imaging studies using [¹8F]FPP(RGD)2 in patient volunteers are now under active investigation.