Synthesis, Characterization, and Biological Evaluation of Radiolabeled Glutamine Conjugated Polymeric Nanoparticles:...

Application of nanoradiopharmaceuticals for molecular imaging has gained worldwide importance for their multifaceted potentials focusing on providing a safe and cost-effective approach. Biodistribution studies on such species are capable of bringing nanomedicine to patients. Current therapeutically available labeling strategies suffer from different limitations, including off-target cytotoxicity and radiolabel release over time. Poly(lactic-co-glycolic acid)(PLGA) nanoparticles are biodegradable carriers for a variety of contrast agents that can be employed in medicine with high loading capacity for multimodal imaging agents. Here, glutamine-conjugated PLGA polymers were used to construct polymeric nanoparticles (G-PNP) similar to unconjugated PLGA nanoparticles (PNP)s formulated for ex vivo cell labeling and in vivo tumor scintigraphy studies. G-PNP/PNP, characterized by Fourier-transform infrared, atomic-force-microscopy, particle-size, and zeta-potential studies, were biocompatible as evaluated by MTT assay. G-PNPs were radiolabeled with ^99mtechnetium (^99mTc) by borohydrite reduction. G-PNPs demonstrated higher cellular uptake than PNPs, with no major cytotoxicity. Radiochemical purity indicated that ^99mTc labeled G-PNP (^99mTc-G-PNP) can form a stable complex with substantial stability in serum with respect to time. Imaging studies showed that ^99mTc-G-PNP significantly accumulated at the C6 glioma cell induced tumor-site in rats. Thus, ^99mTc-G-PNP demonstrated favorable characteristics and imaging potential which may make it a promising tumor imaging nanoprobe as a nanoradiopharmaceutical.