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

Abstract

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 ανβ3 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.

Synthesis and Bioevaluation of Iodine-131 Directly Labeled Cyclic RGD-PEGylated Gold Nanorods for Tumor-Targeted Imaging

“…There has been increasing use of radioisotopes to label nanoparticles, such as positron emitters copper-64 [ 26 ], gallium-67 [ 27 ], and zirconium-89 [ 28 ], and single photon emitters Technetiom-99m [ 3 ] and radioiodine (e.g., iodine-125 [ 29 ], iodine-123, and iodine-131 [ 30 ]). In most conditions, a bifunctional chelator, such as DOTA or HYNIC, must be conjugated to the nanoparticle for radiolabeling.…”

Radiolabeled theranostics: magnetic and gold nanoparticles

“…The engineered NSs exhibited high radiolabeling yield, high stability, specific recognition of U87MG glioma cells and enhanced ex vivo biodistribution ratio from tumor to muscle where the PET and MRI in vivo images supported the ex vivo results. 116 …”

68 Ga-Radiolabeled AGuIX Nanoparticles as Dual-Modality Imaging Agents for PET/MRI-Guided Radiation Therapy

“…Dual-modality contrast agents, such as radiolabeled nanoparticles (NPs), are promising candidates for a number of diagnostic applications, since they combine the advantages of two different imaging modalities, namely PET imaging with MRI. The benefit of such a combination is to more accurately interpret disease and abnormalities in vivo, by exploiting the advantages of each imaging technique, in other words, high sensitivity for PET, high resolution anatomical information for MRI [3][4][5][6].…”