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Objective(s): This study aimed to synthesize Samarium-doped TiO2 nanoparticles (Ti(Sm)O2 NPs) using solvothermal synthesis and evaluate their suitability as targeted imaging agents. The objectives were to enhance the stability and biocompatibility of the nanoparticles by coating them with polymeric materials and assess their imaging capabilities and safety. Materials and Methods: Ti(Sm)O2 NPs were synthesized using the solvothermal method with TiO2, NaOH, and deionized water. The resulting solution was filtered, dried, and processed in a Teflon-lined stainless steel autoclave. The obtained product was washed, dried, and coated with FDA-approved polymers including polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), and carboxymethyl cellulose (CMC). Coating was achieved through a mixing process and subsequent drying. Results: Characterization studies confirmed the desired morphology, crystal structure, optical properties, surface charge, and biocompatibility of the Ti(Sm)O2 NPs. In vivo imaging evaluations demonstrated their excellent imaging capabilities, particularly in distinguishing lung pathologies. Additionally, in vivo toxicity studies confirmed the nanoparticles biocompatibility and safety, with no adverse effects on organ function observed. Conclusion: In this study, Samarium-doped TiO2 nanoparticles WERE successfully synthesized and their potential as targeted imaging agents was evaluated. The coating of the nanoparticles with polymeric materials enhanced their stability and biocompatibility. The nanoparticles exhibited excellent imaging capabilities, particularly in distinguishing lung pathologies. Moreover, they demonstrated biocompatibility and safety in vivo. These findings contribute to the development of advanced contrast agents for biomedical applications, providing effective tools for targeted imaging and improving the diagnosis and monitoring of various lung pathologies.