Longitudinal microPET imaging of brain tumor growth with F-18-labeled RGD peptide.
OBJECTIVE
EMD 121974, a potent cyclic RGD peptide inhibitor of alphav-integrins, demonstrated effectiveness in suppressing brain tumor growth in both preclinical models and phases I/II clinical trials. The ability to non-invasively evaluate alphav-integrin expression provides a novel and unique way to better understand brain tumor angiogenesis in relationship to alphav-integrin expression, and allow for direct assessment of anti-integrin treatment efficacy.


METHODS
We developed a F-18-labeled RGD peptide [F-18]FB-RGD and performed serial microPET imaging scans to follow brain tumor growth and angiogenesis as a function of time in an orthotopic U87MG glioblastoma xenograft model in athymic nude mice.


RESULTS
The tumor was barely visible on microPET at the size of <or=1.5 mm diameter at which time no angiogenesis was evident on histological examination. When tumor started to grow exponentially by day 35 the activity accumulation in the brain tumor also increased accordingly, with best tumor-to-brain contrast seven weeks after inoculation of 10(5) U87MG cells into the mice forebrain.


CONCLUSIONS
Longitudinal microPET imaging and [F-18]FB-RGD provides the sensitivity and resolution to visualize and quantify anatomical variations during brain tumor growth and angiogenesis, most likely through interaction with alphav-integrins expressed on tumor cells and angiogenic tumor vessels.
Chen
Xiaoyuan
X
PET Imaging Science Center, Department of Radiology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA. shawchen@stanford.edu
Park
Ryan
R
Khankaldyyan
Vazgen
V
Gonzales-Gomez
Ignacio
I
Tohme
Michel
M
Moats
Rex A
RA
Bading
James R
JR
Laug
Walter E
WE
Conti
Peter S
PS
D000818:Animals; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007553:Isotope Labeling / Q000379:methods; D051379:Mice; D008819:Mice, Nude; D008968:Molecular Conformation; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D049268:Positron-Emission Tomography; D012680:Sensitivity and Specificity; D014183:Transplantation, Heterologous
D005462:Fluorine Radioisotopes; D009842:Oligopeptides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C047981:arginyl-glycyl-aspartic acid