Technetium-99m Radiolabeled Carboplatin Polymeric Nanoparticles for Imaging and Treatment of Epithelial Ovarian Cancer
Claudiana de Jesus Felismino, Natália Cristina Gomes-da-Silva, Marilia Amável Gomes Soares, Natália Mayumi Andrade Yoshiara, Eduardo Ricci-Junior, Pierre Basílio Almeida Fechine, Pedro Filho Noronha de Souza, Derya Ilem Özdemir, Luciana Magalhães Rebelo Alencar, Ralph Santos-OliveiraIntroduction:
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.