Technetium-99m Radiolabeled Carboplatin Polymeric Nanoparticles for Imaging and Treatment of Epithelial Ovarian Cancer.

INTRODUCTION

Epithelial ovarian cancer (EOC) remains the most lethal gynecological malignancy due to its typically late diagnosis and high recurrence rates. Conventional carboplatin-based therapies are limited by systemic toxicity and chemoresistance. To overcome these barriers, we developed a theranostic system based on Pluronic F-127 nanomicelles encapsulating carboplatin and radiolabeled with technetium-99m (99ᵐTc), aiming for targeted delivery, sustained drug release, and concurrent imaging capability.

MATERIALS AND

METHODS

Carboplatin-loaded Pluronic nanomicelles were prepared by direct dissolution and characterized via dynamic light scattering (DLS), scanning and cryo-electron microscopy (SEM, Cryo-SEM), and energy-dispersive X-ray spectroscopy (EDS). Drug release was assessed by UV-Vis spectrophotometry. In vitro cytotoxicity was evaluated on SK-OV-3 cells using MTT assays. Nanomicelles were radiolabeled with 99ᵐTc, and radiochemical purity/stability were confirmed by TLC. in vivo pharmacokinetics, biodistribution, and biochemical safety profiles were studied in Wistar and Balb/c mice using gamma counting and serum assays.

RESULTS

Nanomicelles exhibited a mean diameter of 274.4 nm with low PDI (0.051), spherical morphology, and high encapsulation efficiency. EDS confirmed homogeneous platinum distribution. The release profile showed a biphasic kinetic with ≈96% cumulative release in 25 h. Cytotoxicity assays revealed time- and dose-dependent effects, with the nanoformulation showing superior or comparable efficacy to free carboplatin. Radiolabeling efficiency exceeded 90% and remained stable for 24 h. Pharmacokinetic modeling indicated a prolonged half-life (12.73 h), extensive volume of distribution, and slow systemic clearance. Biodistribution favored renal elimination with minimal off-target accumulation. Biochemical analyses indicated no significant hepatotoxicity or nephrotoxicity, though elevated lipase suggested potential pancreatic involvement.

DISCUSSION: The PLU-carboplatin nanomicelles demonstrated physicochemical robustness, sustained-release kinetics, and effective in vitro cytotoxicity. Radiolabeling with 99ᵐTc enabled simultaneous biodistribution tracking, affirming their theranostic potential. Pharmacokinetic and safety profiles support the feasibility of this nanoformulation as a targeted therapeutic and diagnostic platform for EOC, warranting further translational development.

CONCLUSION

Technetium-99m radiolabeled Pluronic F-127 nanomicelles encapsulating carboplatin exhibit desirable theranostic characteristics, including structural integrity, controlled drug release, dual cytotoxic and imaging capacity, and minimal systemic toxicity. These findings position the system as a promising candidate for targeted therapy and real-time monitoring in epithelial ovarian cancer and justify its advancement to more complex preclinical models.