Combined magnetic resonance and optical imaging of head and neck tumor xenografts using Gadolinium-labelled phosphorescent polymeric nanomicelles.
BACKGROUND
The overall objective of this study was to develop a nanoparticle formulation for dual modality imaging of head and neck cancer. Here, we report the synthesis and characterization of polymeric phospholipid-based nanomicelles encapsulating near-infrared (NIR) phosphorescent molecules of Pt(II)-tetraphenyltetranaphthoporphyrin [Pt(TPNP)] and surface functionalized with gadolinium [Pt(TPNP)-Gd] for combined magnetic resonance imaging (MRI) and NIR optical imaging applications.


METHODS
Dynamic light scattering, electron microscopy, optical spectroscopy and MR relaxometric measurements were performed to characterize the optical and magnetic properties of nanoparticles in vitro. Subsequently, in vivo imaging experiments were carried out using nude mice bearing primary patient tumor-derived human head and neck squamous cell carcinoma xenografts.


RESULTS
The nanomicelles were ~100 nm in size and stable in aqueous suspension. T1-weighted MRI and relaxation rate (R1 = 1/T1) measurements carried out at 4.7 T revealed enhancement in the tumor immediately post injection with nanomicelles, particularly in the tumor periphery which persisted up to 24 hours post administration. Maximum intensity projections (MIPs) generated from 3D T1-weighted images also demonstrated visible enhancement in contrast within the tumor, liver and blood vessels. NIR optical imaging performed (in vivo and ex vivo) following completion of MRI at the 24 h time point confirmed tumor localization of the nanoparticles. The large spectral separation between the Pt(TPNP) absorption (~700 nm) and phosphorescence emission (~900 nm) provided a dramatic decrease in the level of background, resulting in high contrast optical (NIR phosphorescence) imaging.


CONCLUSIONS
In conclusion, Pt(TPNP)-Gd nanomicelles exhibit a high degree of tumor-avidity and favorable imaging properties that allow for combined MR and optical imaging of head and neck tumors. Further investigation into the potential of Pt(TPNP)-Gd nanomicelles for combined imaging and therapy of cancer is currently underway.
Institute for Lasers, Photonics and Biophotonics, SUNY at Buffalo, Buffalo, New York, USA.
Rajiv
R
Kumar
Tymish Y
TY
Ohulchanskyy
Steve G
SG
Turowski
Mark E
ME
Thompson
Mukund
M
Seshadri
Paras N
PN
Prasad
D000818:Animals; D002277:Carcinoma / Q000175:diagnosis / Q000378:metabolism; D002294:Carcinoma, Squamous Cell; D005260:Female; D005682:Gadolinium / Q000493:pharmacokinetics; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000378:metabolism; D006801:Humans; D049408:Luminescent Agents / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D008823:Micelles; D008954:Models, Biological; D053758:Nanoparticles; D018307:Neoplasms, Squamous Cell / Q000175:diagnosis / Q000378:metabolism; D055096:Optical Devices; D011108:Polymers / Q000493:pharmacokinetics; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D000077195:Squamous Cell Carcinoma of Head and Neck; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D049408:Luminescent Agents; D008823:Micelles; D011108:Polymers; D005682:Gadolinium