Imaging of Vx-2 rabbit tumors with alpha(nu)beta3-integrin-targeted 111In nanoparticles.
Earlier tumor detection can improve 5-year survival of patients, particularly among those presenting with cancers less than 1 cm in diameter. alpha(nu)beta(3)-Targeted (111)In nanoparticles (NP) were developed and studied for detection of tumor angiogenesis. Studies were conducted in New Zealand white rabbits implanted 12 days earlier with Vx-2 tumor. alpha(nu)beta(3)-Targeted (111)In/NP bearing approximately 10 (111)In/NP vs. approximately 1 (111)In/NP nuclide payloads were compared to nontargeted radiolabeled control particles. In vivo competitive binding studies were used to assess ligand-targeting specificity. alpha(nu)beta(3)-Integrin-targeted NP with approximately 10 (111)In/NP provided better (p < 0.05) tumor-to-muscle ratio contrast (6.3 +/- 0.2) than approximately 1 (111)In/NP (5.1 +/- 0.1) or nontargeted particles with approximately 10 (111)In/NP (3.7 +/- 0.1) over the initial 2-hr postinjection. At 18 hr, mean tumor activity in rabbits receiving alpha(nu)beta(3)-integrin-targeted NP was 4-fold higher than the nontargeted control. Specificity of the NP for the tumor neovasculature was supported by in vivo competition studies and by fluorescence microscopy of alpha(nu)beta(3)-targeted fluorescent-labeled NP. Biodistribution studies revealed that the primary clearance organ in rabbits as a %ID/g tissue was the spleen. Circulatory half-life (t(1/2)beta) was estimated to be approximately 5 hr using a 2-compartment model. alpha(nu)beta(3)-Targeted (111)In perfluorocarbon NP may provide a clinically useful tool for sensitively detecting angiogenesis in nascent tumors, particularly in combination with secondary high-resolution imaging modalities, such as MRI.
Hu
Grace
G
Department of Medicine, Division of Cardiology, Washington University Medical School, St. Louis, MO, USA.
Lijowski
Michal
M
Zhang
Huiying
H
Partlow
Kathryn C
KC
Caruthers
Shelton D
SD
Kiefer
Garry
G
Gulyas
Gyongyi
G
Athey
Phillip
P
Scott
Michael J
MJ
Wickline
Samuel A
SA
Lanza
Gregory M
GM
D000818:Animals; D007205:Indium Radioisotopes; D039302:Integrin alphaVbeta3 / Q000032:analysis*; D008279:Magnetic Resonance Imaging; D008297:Male; D053758:Nanoparticles; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000000981:diagnostic imaging; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging*; D011817:Rabbits; D011877:Radionuclide Imaging
D007205:Indium Radioisotopes; D039302:Integrin alphaVbeta3