Small particulate gadolinium oxide and gadolinium oxide albumin microspheres as multimodal contrast and therapeutic agents

Rationale and objective: To prepare and characterize new particulate contrast media, small particulate gadolinium oxide (SPGO) and gadolinium oxide albumin microspheres (GOAM), as prototype multimodal imaging and therapeutic agents. Methods: SPGO was purchased from Alfa Aesar Inc. (Ward Hill, MA). GOAM were synthesized via ultrasonic irradiation using SPGO and 5% bovine serum albumin in aqueous solution. SPGO and GOAM were characterized by size, concentration, structure, and gadolinium content. Their relaxivity at high magnetic field strength and x-ray attenuating abilities were evaluated in 0.4% agar gel at room temperature. Results: SPGO were confirmed to be 20-40 nm in diameter. GOAM have an average size of 2 to 5 mum and show a relatively homogeneous distribution of SPGO within the albumin microspheres. T1 and T2 relaxivity of GOAM was 6.7 seconds(-1) mmol/L-1 and 38.5 seconds(-1) mmol/L-1, respectively, while that of SPGO was 0.2 seconds(-1) mmol/L-1 and 6.8 seconds(-1) mmol/L-1, respectively. At 0, 0.004, 0.16, 4.0, and 16.0 mmol/L SPGO, x-ray attenuation values were measured at 2.11, 3.48, 7.06, 39.83, and 187.33 Hounsfield units, respectively. Conclusions: Use of SPGO and SPGO encapsulated in non-heat-hardened albumin microspheres (GOAM) represents a new approach. SPGO and GOAM have suitable physicochemical properties to warrant further biophysical and animal studies and reevaluation of toxicity limitations.