Reproducibility study of [(18)F]FPP(RGD)2 uptake in murine models of human tumor xenografts.
OBJECTIVE
An (18)F-labeled PEGylated arginine-glycine-aspartic acid (RGD) dimer {[(18)F]FPP(RGD)(2)} has been used to image tumor α(v)β(3) integrin levels in preclinical and clinical studies. Serial positron emission tomography (PET) studies may be useful for monitoring antiangiogenic therapy response or for drug screening; however, the reproducibility of serial scans has not been determined for this PET probe. The purpose of this study was to determine the reproducibility of the integrin α(v)β(3)-targeted PET probe, [(18)F]FPP(RGD)(2,) using small animal PET.


METHODS
Human HCT116 colon cancer xenografts were implanted into nude mice (n = 12) in the breast and scapular region and grown to mean diameters of 5-15 mm for approximately 2.5 weeks. A 3-min acquisition was performed on a small animal PET scanner approximately 1 h after administration of [(18)F]FPP(RGD)(2) (1.9-3.8 MBq, 50-100 μCi) via the tail vein. A second small animal PET scan was performed approximately 6 h later after reinjection of the probe to assess for reproducibility. Images were analyzed by drawing an ellipsoidal region of interest (ROI) around the tumor xenograft activity. Percentage injected dose per gram (%ID/g) values were calculated from the mean or maximum activity in the ROIs. Coefficients of variation and differences in %ID/g values between studies from the same day were calculated to determine the reproducibility.


RESULTS
The coefficient of variation (mean±SD) for %ID(mean)/g and %ID(max)/g values between [(18)F]FPP(RGD)(2) small animal PET scans performed 6 h apart on the same day were 11.1 ± 7.6% and 10.4 ± 9.3%, respectively. The corresponding differences in %ID(mean)/g and %ID(max)/g values between scans were -0.025 ± 0.067 and -0.039 ± 0.426. Immunofluorescence studies revealed a direct relationship between extent of α(ν)β(3) integrin expression in tumors and tumor vasculature with level of tracer uptake. Mouse body weight, injected dose, and fasting state did not contribute to the variability of the scans; however, consistent scanning parameters were necessary to ensure accurate studies, in particular, noting tumor volume, as well as making uniform: the time of imaging after injection and the ROI size. Reanalysis of ROI placement displayed variability for %ID(mean)/g of 6.6 ± 3.9% and 0.28 ± 0.12% for %ID(max)/g.


CONCLUSIONS
[(18)F]FPP(RGD)(2) small animal PET mouse tumor xenograft studies are reproducible with relatively low variability.
Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford University, 1201 Welch Road, Lucas Center, P020A, Stanford, CA 94305-5484, USA.
Edwin
E
Chang
Shuangdong
S
Liu
Gayatri
G
Gowrishankar
Shahriar
S
Yaghoubi
James Patrick
JP
Wedgeworth
Frederick
F
Chin
Dietmar
D
Berndorff
Volker
V
Gekeler
Sanjiv S
SS
Gambhir
Zhen
Z
Cheng
D000818:Animals; D001692:Biological Transport; D002471:Cell Transformation, Neoplastic; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D007267:Injections; D051379:Mice; D009842:Oligopeptides / Q000008:administration & dosage / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000378:metabolism*; D049268:Positron-Emission Tomography; D015203:Reproducibility of Results; D013623:Tail / Q000098:blood supply; D047368:Tumor Burden; D014680:Veins
D009842:Oligopeptides; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid