Evaluation of radiogallium-labeled, folate-embedded superparamagnetic nanoparticles in fibrosarcoma-bearing mice.

ABSTRACT

CONTEXT Elevated expression of the folate receptor (FR) occurs in many human malignancies. Thus, folate targeting is widely utilized in drug delivery purposes specially using nano-radioactive agents. AIMS: In this work, we report production and biological evaluation of gallium-67 labeled superparamagnetic iron oxide nanoparticles, embedded by folic acid ( 67 Ga-SPION-folate) complex especially in tumor-bearing mice for tumor imaging studies. SETTINGS AND DESIGN: The structure of SPION-folate was confirmed by X-ray diffraction (XRD), transmission electron microscopy (TEM) and foureir transform infrared spectroscopy (FT-IR) analyses. The radiolabeled SPION-folate formation was confirmed by instant thin layer chromatography (ITLC). Tumor induction was performed by the use of poly-aromatic hydrocarbon injection in rodents as reported previously. MATERIALS AND METHODS: [ 67 Ga]-SPION-folate was shown to possess a particle size of ≈ 5-10 nm using instrumental methods followed by ITLC test. Biocompatibility of the compound was investigated using an 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay followed by stability tests and tumor accumulation studies in fibrosarcoma-bearing mice after subcutaneous (s.c.) application. STATISTICAL ANALYSIS USED All values were expressed as mean ± standard deviation (mean ± SD) and the data were compared using Student t-test. Statistical significance was defined as P<0.05. RESULTS: [ 67 Ga]-SPION-folate was prepared by a modified co-precipitation method possessing a particle size of ≈ 5-10 nm using instrumental methods (>95% radiochemical purity). Biodistribution studies demonstrated tumorblood, tumorbone and tumormuscle ratios of 4.23, 4.98 and 11.54 respectively after 24 h. CONCLUSIONS: Due to the nano-scale size and high-penetrative property of the developed folate-containing nano-complex, this system can be an interesting drug delivery modality with therapeutic applications and folate receptor-targeting behavior, while possessing paramagnetic properties for thermotherapy.