First Experience with Clinical-Grade [18F]FPP(RGD)2: An Automated Multi-step Radiosynthesis for Clinical PET Studies

Purpose: A reliable and routine process to introduce a new F-18-labeled dimeric RGD-peptide tracer ([F-18]FPP(RGD)(2)) for noninvasive imaging of alpha(v)beta(3) expression in tumors needed to be developed so the tracer could be evaluated for the first time in man. Clinical-grade [F-18]FPP (RGD)(2) was screened in mouse prior to our first pilot study in human. Procedures: [F-18]FPP(RGD)(2) was synthesized by coupling 4-nitrophenyl-2-[F-18]Fluoropropionate ([F-18] NPE) with the dimeric RGD-peptide (PEG3-c(RGDyK)(2)). Imaging studies with [F-18]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, [F-18]FPP(RGD)(2) was obtained with RCYs of 16.9 +/- 2.7% (n=8, EOB) and specific radioactivity of 114 +/- 72 GBq/mu mol (3.08 +/- 1.95 Ci/mu mol; 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 [F-18]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 [F-18]FPP(RGD)(2) was established. PET imaging in a healthy human volunteer illustrates that [F-18]FPP(RGD)(2) possesses desirable pharmacokinetic properties for clinical noninvasive imaging of alpha(v)beta(3) expression. Further imaging studies using [F-18]FPP(RGD)(2) in patient volunteers are now under active investigation.