Initial in vitro and in vivo assessment of Au@DTDTPA-RGD nanoparticles for Gd-MRI and 68Ga-PET dual modality imaging

Gadolinium chelate coated gold nanoparticles (Au@DTDTPA) can be applied as contrast
agents for both in vivo X-ray and magnetic resonance imaging. In this work, our aim
was to radiolabel and evaluate this gold nanoparticle with Ga-68, in order to produce
a dual modality PET/MRI imaging probe. For a typical preparation of 68Ga-labeled nanoparticles,
the Au@DTDTPA nanoparticles (Au@DTDTPA/Au@DTDTPA-RGD) were mixed with ammonium acetate
buffer, pH 5 and 40 MBq of 68Ga eluate. The mixture was then incubated for 45 min
at 65 ÅãC. Radiochemical purity was determined by ITLC. In vitro stability of both
radiolabeled species was assessed in saline and serum. In vitro cell binding experiments
were performed on integrin ???3 receptor-positive U87MG cancer cells. Non-specific
Au@DTDTPA was used for comparison. Ex vivo biodistribution studies and in vivo PET
and MRI imaging studies in U87MG tumor-bearing SCID mice followed. The Au@DTDTPA nanoparticles
were labeled with Gallium-68 at high radiochemical yield (95%) and were stable at
RT, and in the presence of serum, for up to 3 h. The cell binding assay on U87MG glioma
cells proved that 68Ga-cRGD-Au@DTDTPA had specific recognition for these cells. Biodistribution
studies in U87MG tumor-bearing SCID mice showed that the tumor to muscle ratio increased
from 1 to 2 h p.i. (3,71 ± 0.22 and 4,69 ± 0.09 respectively), showing a clear differentiation
between the affected and the non-affected tissue. The acquired PET and MRI images
were in accordance to the ex vivo biodistribution results. The preliminary results
of this study warrant the need for further development of Au@DTDTPA nanoparticles
radiolabeled with Ga-68, as possible dual-modality PET/MRI imaging agents.