^۹۹mTc-labeled anionic linear-globular dendrimers conjugated with l-arginine as a novel radiotracer for single photon emission computed tomography of breast tumor xenografts

Objective(s): Dendrimers are promising molecular imaging platforms because of their multivalency and tunable surfaces. This study synthesized a PEGylated anionic linear-globular dendrimer conjugated with L-arginine and labeled with technetium-۹۹m (⁹⁹ᵐTc-DND-G۲-Arg) as a targeted SPECT tracer for breast cancer.Materials and Methods: G۲-dendrimers were synthesized via divergent esterification and conjugated to L-arginine using carbodiimide chemistry. Physicochemical characterization was performed using FTIR, FE-SEM, DLS, and LC-MS. Cell compatibility was assessed by MTT assay in Vero cells. Radiochemical purity/stability were assessed by radio thin layer chromatography. In vivo biodistribution and SPECT imaging were conducted at ۵, ۳۰, and ۱۲۰ minutes post-injection in BALB/c mice with ۴T۱ tumors. Kinetic behavior was analyzed using a two-compartment model.Results: FTIR and LC-MS analyses verified successful L-arginine conjugation to G۲-PEG-citrate-ALGD. The spherical nanoparticles (FE-SEM: ۱۳۴.۹۱ ± ۱۵.۰۱ nm; DLS: ۲۰۲.۴ nm; zeta potential: -۷.۳ mV) exhibited excellent cytocompatibility (>۹۵% viability). The highly pure radiolabeled conjugate (۹۹.۶۸%) also remained stable, exceeding ۹۵% over one physical half-life and retaining ۸۰-۸۵% stability at ۴۸ hours in PBS and serum. In vivo studies revealed specific tumor uptake (۰.۸۷ ± ۰.۱۹ %ID/g), which decreased by ۳۱% after L-arginine blocking (p < ۰.۰۵). SPECT imaging demonstrated a strong early tumor uptake (SUVmax ۴.۸ at ۳۰ min) with rapid blood clearance, while kinetic modeling indicated fast tumor influx, efficient irreversible trapping, and minimal efflux.Conclusion: ⁹⁹ᵐTc-DND-G۲-Arg demonstrates specific tumor targeting, favorable pharmacokinetics, and excellent in vivo stability in a preclinical xenograft model, supporting further investigation as a potential SPECT radiotracer for imaging arginine-enriched breast cancers.

کلیدواژه ها:

Technetium ، Dendrimers ، Arginine ، Radionuclide Imaging ، Breast neoplasms