title: (18)F-FPPRGD2 PET/CT: pilot phase evaluation of breast cancer patients.
abstract: OBJECTIVE
  To present data from the first prospective pilot phase trial of breast cancer participants imaged with fluorine 18 ((18)F)-2-fluoropropionyl-labeled PEGylated dimeric arginine-glycine-aspartic acid ( RGD arginine-glycine-aspartic acid ) peptide (PEG3-E[c{ RGD arginine-glycine-aspartic acid yk}]2) ( FPPRGD2 2-fluoropropionyl labeled PEGylated dimeric RGD peptide (PEG3-E[c{RGDyk}]2) ), a radiopharmaceutical agent used in positron emission tomographic (PET) imaging.
  
  
  METHODS
  The local institutional review board approved the HIPAA-compliant protocol. Written informed consent was obtained from each patient. Eight women (age range, 44-67 years; mean age, 54.3 years ± 8.8 [standard deviation]) with newly diagnosed or recurrent breast cancer were recruited between November 2010 and February 2011. (18)F- FPPRGD2 2-fluoropropionyl labeled PEGylated dimeric RGD peptide (PEG3-E[c{RGDyk}]2) PET/computed tomographic (CT) and (18)F-fluorodeoxyglucose ( FDG fluorine 18 fluorodeoxyglucose ) PET/CT examinations were performed within 3 weeks of each other. Dynamic (18)F- FPPRGD2 2-fluoropropionyl labeled PEGylated dimeric RGD peptide (PEG3-E[c{RGDyk}]2) PET and two whole-body static (18)F- FPPRGD2 2-fluoropropionyl labeled PEGylated dimeric RGD peptide (PEG3-E[c{RGDyk}]2) PET/CT scans were obtained. During this time, vital signs and electrocardiograms were recorded at regular intervals. Blood samples were obtained before the injection of (18)F- FPPRGD2 2-fluoropropionyl labeled PEGylated dimeric RGD peptide (PEG3-E[c{RGDyk}]2) and at 24 hours and 1 week after injection to evaluate for toxicity. A nonparametric version of multivariate analysis of variance was used to assess the safety outcome measures simultaneously across time points. A paired two-sample t test was performed to compare the maximum standardized uptake values ( SUVmax maximum standardized uptake value ).
  
  
  RESULTS
  (18)F- FPPRGD2 2-fluoropropionyl labeled PEGylated dimeric RGD peptide (PEG3-E[c{RGDyk}]2) was well tolerated, without noticeable changes in vital signs, on electrocardiograms, or in laboratory values. A total of 30 lesions were evaluated at (18)F- FDG fluorine 18 fluorodeoxyglucose PET/CT and (18)F- FPPRGD2 2-fluoropropionyl labeled PEGylated dimeric RGD peptide (PEG3-E[c{RGDyk}]2) PET/CT. The primary breast lesions had (18)F- FPPRGD2 2-fluoropropionyl labeled PEGylated dimeric RGD peptide (PEG3-E[c{RGDyk}]2) uptake with SUVmax maximum standardized uptake value of 2.4-9.4 (mean, 5.6 ± 2.8) 60 minutes after injection, compared with (18)F- FDG fluorine 18 fluorodeoxyglucose uptake with SUVmax maximum standardized uptake value of 2.8-18.6 (mean, 10.4 ± 7.2). Metastatic lesions also showed (18)F- FPPRGD2 2-fluoropropionyl labeled PEGylated dimeric RGD peptide (PEG3-E[c{RGDyk}]2) uptake, with SUVmax maximum standardized uptake value of 2.4-9.7 (mean, 5.0 ± 2.3) at 60 minutes, compared with (18)F- FDG fluorine 18 fluorodeoxyglucose uptake with SUVmax maximum standardized uptake value of 2.2-14.6 (mean, 6.6 ± 4.2).
  
  
  CONCLUSIONS
  Data from this pilot phase study suggest that (18)F- FPPRGD2 2-fluoropropionyl labeled PEGylated dimeric RGD peptide (PEG3-E[c{RGDyk}]2) is a safe PET radiopharmaceutical agent. Evaluation of (18)F- FPPRGD2 2-fluoropropionyl labeled PEGylated dimeric RGD peptide (PEG3-E[c{RGDyk}]2) in participants with breast cancer demonstrated significant uptake in the primary lesion and in the metastases. Larger cohorts are required to confirm these preliminary findings.
authors.affiliation: From the Division of Nuclear Medicine and Molecular Imaging (A.I., C.M., E.M.), Molecular Imaging Program at Stanford (B.S., F.T.C.), Division of Medical Oncology (M.L.T.), and Departments of Radiology, Bioengineering, and Materials Science and Engineering (S.S.G.), Stanford University Medical Center, 300 Pasteur Dr, Room H-0101, Stanford, CA 94305.
authors.forename: Andrei
authors.initials: A
authors.lastname: Iagaru
authors.forename: Camila
authors.initials: C
authors.lastname: Mosci
authors.forename: Bin
authors.initials: B
authors.lastname: Shen
authors.forename: Frederick T
authors.initials: FT
authors.lastname: Chin
authors.forename: Erik
authors.initials: E
authors.lastname: Mittra
authors.forename: Melinda L
authors.initials: ML
authors.lastname: Telli
authors.forename: Sanjiv Sam
authors.initials: SS
authors.lastname: Gambhir
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000000981:diagnostic imaging*; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008875:Middle Aged; D064847:Multimodal Imaging; D009842:Oligopeptides; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D012680:Sensitivity and Specificity; D014057:Tomography, X-Ray Computed
chemical_list: D005462:Fluorine Radioisotopes; D009842:Oligopeptides; D019275:Radiopharmaceuticals; C047981:arginyl-glycyl-aspartic acid