First experience with clinical-grade ([18F]FPP(RGD₂): an automated multi-step radiosynthesis for clinical PET studies.

Abstract

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)β₃ 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)β₃ expression. Further imaging studies using [¹⁸F]FPP(RGD)₂ in patient volunteers are now under active investigation.

• Authors: Frederick T Chin, Bin Shen, Shuanglong Liu, Rhona A Berganos, Edwin Chang, Erik Mittra, Xiaoyuan Chen, Sanjiv S Gambhir
• Journal: Molecular imaging and biology (Mol Imaging Biol) Vol. 14 Issue 1 Pg. 88-95 (Feb 2012) ISSN: 1860-2002 [Electronic] United States
• PMID: 21400112 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• FPP(RGD)2
• Fluorine Radioisotopes
• Oligopeptides
• Peptides, Cyclic
• Radiopharmaceuticals
• arginyl-glycyl-aspartic acid

Topics

• Adult
• Animals
• Female
• Fluorine Radioisotopes (chemistry, pharmacokinetics)
• Humans
• Mice
• Mice, Nude
• Oligopeptides (chemistry, pharmacokinetics)
• Peptides, Cyclic (chemical synthesis, chemistry, pharmacokinetics)
• Positron-Emission Tomography (methods)
• Radiopharmaceuticals (chemical synthesis, chemistry, pharmacokinetics)
• Tissue Distribution