First experience with clinical-grade [ 18F]FPP (RGD) 2

An automated multi-step radiosynthesis for clinical PET studies

Frederick T. Chin, Bin Shen, Shuanglong Liu, Rhona A. Berganos, Edwin Chang, Erik Mittra, Xiaoyuan Chen, Sanjiv S. Gambhir

Research output: Contribution to journalArticle

57 Citations (Scopus)

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 α vβ 3 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 (PEG 3-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 vβ 3 expression. Further imaging studies using [ 18F]FPP(RGD) 2 in patient volunteers are now under active investigation.

Original languageEnglish (US)
Pages (from-to)88-95
Number of pages8
JournalMolecular Imaging and Biology
Volume14
Issue number1
DOIs
StatePublished - Feb 1 2012
Externally publishedYes

Fingerprint

Radioactivity
Healthy Volunteers
Clinical Studies
FPP(RGD)2
Volunteers
Neoplasms
Urinary Bladder
Neck
Thorax
Pharmacokinetics
Head
Neoplasm Metastasis
Kidney
Growth
arginyl-glycyl-aspartic acid
4-nitrophenyl 2-fluoropropionate

Keywords

  • [ F]FPP(RGD)
  • Automated radiosynthesis
  • Clinical PET
  • Integrins
  • Oncology
  • Peptides
  • Radiopharmaceuticals
  • Tumor angiogenesis

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

First experience with clinical-grade [ 18F]FPP (RGD) 2 : An automated multi-step radiosynthesis for clinical PET studies. / Chin, Frederick T.; Shen, Bin; Liu, Shuanglong; Berganos, Rhona A.; Chang, Edwin; Mittra, Erik; Chen, Xiaoyuan; Gambhir, Sanjiv S.

In: Molecular Imaging and Biology, Vol. 14, No. 1, 01.02.2012, p. 88-95.

Research output: Contribution to journalArticle

Chin, Frederick T. ; Shen, Bin ; Liu, Shuanglong ; Berganos, Rhona A. ; Chang, Edwin ; Mittra, Erik ; Chen, Xiaoyuan ; Gambhir, Sanjiv S. / First experience with clinical-grade [ 18F]FPP (RGD) 2 : An automated multi-step radiosynthesis for clinical PET studies. In: Molecular Imaging and Biology. 2012 ; Vol. 14, No. 1. pp. 88-95.
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AU - Shen, Bin

AU - Liu, Shuanglong

AU - Berganos, Rhona A.

AU - Chang, Edwin

AU - Mittra, Erik

AU - Chen, Xiaoyuan

AU - Gambhir, Sanjiv S.

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N2 - Purpose: A reliable and routine process to introduce a new 18F-labeled dimeric RGD-peptide tracer ([ 18F]FPP(RGD) 2) for noninvasive imaging of α vβ 3 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 (PEG 3-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 vβ 3 expression. Further imaging studies using [ 18F]FPP(RGD) 2 in patient volunteers are now under active investigation.

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