Detection of targeted perfluorocarbon nanoparticle binding using 19F diffusion weighted MR spectroscopy

Real‐time detection of targeted contrast agent binding is challenging due to background signal from unbound agent. 19F diffusion weighted MR spectroscopy (DWS) could selectively detect binding of angiogenesis‐targeted perfluorocarbon nanoparticles in vivo. Transgenic K14‐HPV16 mice with epidermal squamous carcinomas exhibiting up‐regulated neovasculature were used, with nontransgenic littermates as controls. Mice were treated with αvβ3‐integrin targeted perfluorocarbon nanoparticles. 19F DWS (b‐values from 0 to 16,000 s/mm2) was performed on mouse ears in vivo at 11.74 Tesla. Progressive decay of 19F signal with increased diffusion weighting at low b‐values (< 1500 s/mm2) was observed in ears of both K14‐HPV16 and control mice, demonstrating suppression of background 19F signal from unbound nanoparticles in the blood. Much of the 19F signal from ears of K14‐HPV16 mice persisted at high b‐values, indicating a stationary signal source, reflecting abundant nanoparticle binding to angiogenesis. 19F signal in controls decayed completely at high b‐values (> 1500 s/mm2), reflecting a moving signal source due to absence of angiogenesis (no binding sites). Estimated ADCs of nanoparticles in K14‐HPV16 and control mice were 33.1 ± 12.9 μm2/s and 19563 ± 5858 μm2/s (p < 0.01). In vivo 19F DWS can be used for specific detection of bound perfluorocarbon nanoparticles by selectively suppressing background 19F signal from nanoparticles flowing in blood. Magn Reson Med 60:1232–1236, 2008. © 2008 Wiley‐Liss, Inc.