Gd-chelates have widely been used clinically as positive agents for MRI. But they suffer from fast elimination and non-specific biodistribution. Compared with Gd-chelates, Gadolinium oxide(Gd2O3) nanoparticles(NPs) have shown advantages such as comparatively high T1 relaxivity, a prolonged blood half-life, and greater opportunities for functionalization.1 In this report, Bombesin(BBN)-assembled fluorescein-conjugated Gd2O3 NPs were synthesized and evaluated for targeted MR/optical bimodal imaging, to develop a Gd2O3-based targeted nanoprobe which is efficient for earlier tumor detectionGd2O3 NPs were conjugated with 5(6)-carboxyfluorescein (FI) for fluorescence and modified with polyethylene glycol (PEG) for hydrophilic surface. In addition, to target cancer cells, Gd2O3 NPs were conjugated with Bombesin(7-14) that specifically bind to the Gastrin Releasing Peptide receptor (GRPr) of tumor cell (Fig.1).2 The chemical and physical properties of the NPs were investigated with transmission electron microscopy (TEM), FT-IR spectra, Thermal gravimetric analysis (TGA) and MRI. Cell viability of PC-3 cells was determined by MTT assay. To confirm the specificity and efficiency of cellular uptake, targeted Gd2O3-FI-PEG-BBN NPs were evaluated with GRPr positive PC-3 cells, which was observed by fluorescence microscopy, flow cytometry and MRI in vitro. Gd2O3-FI-PEG NPs without bombesin-modified NPs were tested as non-targeted control. PC-3 tumor-bearing mice were injected through the tail vein with Gd2O3-FI-PEG-BBN or Gd2O3-FI-PEG (500uL，4mmol/L of Gd concentration) . The contrast enhancement in the tumor site was observed by MRI and optical imaging respectively before and 1h, 2h, 4h post administration. TSE T1-weigthed coronal images were acquired with a 3.0 T clinical MR scanner(Achieva TX, Philips Healthcare, Netherlands) using an animal coil. Sequence parameters were as follow: TR= 500ms, TE = 10 ms, FOV = 100 × 100× 17mm，slice=8，slice thickness=2 mm, gap=0mm，NSA= 3. The data are expressed as mean±S.D. Independent-Sample T-Test was used to analyze the difference of enhancement ratio among groups with SPSS software (SPSS version 16.0, IBM Corporation, USA). P<0.05 was considered as significant difference. After in vivo imaging, tumors were resected from the sacrificed mice for fluorescence immunohistochemistry.Results of vitro studies confirmed that BBN-assembled Gd2O3 nanoprobe has an average diameter of 50 nm and exhibit high relaxivity(Figure 1) . The cell viability (24h or 48h) of Gd2O3-FI-PEG-BBN and Gd2O3-FI-PEG were all above 80% in test dosage range(Gd concentration 0-8mM)(Figure 2) . In the cellular uptake experiments, Gd2O3-FI-PEG-BBN NPs was absorbed by GRPr positive PC-3 cell, while no obviously uptake was observed for Gd2O3-FI-PEG NPs（Figure 3）. BBN-assembled Gd2O3 nanoprobe exhibited better binding affinity to targeted cells than non-modified Gd2O3. A relatively significant enhancement of T1 signal intensity was appeared in the tumor site of mice administrated Gd2O3-FI-PEG-BBN. In comparison, the T1 signal enhancement of tumor in mice received Gd2O3-FI-PEG was not so significant. Peak value of signal intensity appeared at about 2h post administration. The enhancement ratios of Gd2O3-FI-PEG-BBN and Gd2O3-FI-PEG were 27.95±5.86% and 4.02±2.24% (n=5), respectively. Optical imaging and immunohistochemical analysis of tumor tissue confirmed the enhanced accumulation of the targeted nanoprobe in tumor site(Figure 4) . Bombesin (BBN), as an analog of gastrin-releasing peptide (GRP), is able to bind to GRP receptor that is overexpressed in several human tumors, particularly prostate cancer. Although some studies have reported the use of BBN-assembled nanomaterial as a probe for PET or optical imaging successfully, there is still a lack of systematical studies on BBN-assembled nanomaterial as positive MRI contrast agent. 3,4 The result of MTT Assay is an indication of their excellent biocompatibility without release of dissociated gadolinium in vitro. These results indicated that BBN-assembled Gd2O3 could significantly enhance the uptake in GRPr positive tumors.5 In vivo MR imaging study, Gd2O3-FI-PEG-BBN demonstrated considerable signal enhancement in tumor with a long blood circulation time. It was related to the PEG coating in the particle surface which could avoid the recognition by reticuloendothelial system (RES) and prolong the circulating time.6In this report, BBN-assembled and FI-conjugated Gd2O3 nanoprobe was designed and synthesized. These results in vitro and vivo study clearly indicate the multifunctional BBN-assembled nanoprobe Gd2O3 is expected to be applied to bimodal imaging and drug delievery of GRPr positive tumor.