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

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Abstract

Purpose

A reliable and routine process to introduce a new 18F-labeled dimeric RGD-peptide tracer ([18F]FPP(RGD)2) for noninvasive imaging of αvβ3 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 αvβ3 expression. Further imaging studies using [18F]FPP(RGD)2 in patient volunteers are now under active investigation.

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Acknowledgments

This research was financially supported by an NCI ICMIC P50 CA114747 Grant (SSG) and the Doris Duke foundation (SSG). We are also grateful to GE Medical Systems and Dr. David Dick for their technical support.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

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Correspondence to Frederick T. Chin.

Additional information

Bin Shen and Shuanglong Liu contributed equally to this work.

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Chin, F.T., Shen, B., Liu, S. et al. First Experience with Clinical-Grade [18F]FPP(RGD)2: An Automated Multi-step Radiosynthesis for Clinical PET Studies. Mol Imaging Biol 14, 88–95 (2012). https://doi.org/10.1007/s11307-011-0477-3

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  • DOI: https://doi.org/10.1007/s11307-011-0477-3

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