Nanomedicine Journal

Nanomedicine Journal

99mTc-labeled anionic linear-globular dendrimers conjugated with l-arginine as a novel radiotracer for single photon emission computed tomography of breast tumor xenografts

Articles in Press

Document Type : Research Paper

Authors
Parham Karimi 1
Mehdi Shafiee Ardestani 1, 2
Massoud Amanlou 3
Tahereh Zadeh Mehrizi 4
Mehdi Mirzaei 5
Ahmad Javanmard 6
Seyed Mohsen Asghari 7
1 Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
2 Research Center for Nuclear Medicine, Shariati Hospital, Tehran, Iran
3 Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
4 Health Management and Economics Research Center, Health Management Research Institute, Iran University of Medical Sciences, Tehran, Iran
5 Ministry of Health and Medical Education, Tehran, Iran
6 Student Research Committee, Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
7 Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
10.22038/nmj.2026.96242.2436
Abstract
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-99m (⁹⁹ᵐTc-DND-G2-Arg) as a targeted SPECT tracer for breast cancer.
Materials and Methods: G2-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 5, 30, and 120 minutes post-injection in BALB/c mice with 4T1 tumors. Kinetic behavior was analyzed using a two-compartment model.
Results: FTIR and LC-MS analyses verified successful L-arginine conjugation to G2-PEG-citrate-ALGD. The spherical nanoparticles (FE-SEM: 134.91 ± 15.01 nm; DLS: 202.4 nm; zeta potential: -7.3 mV) exhibited excellent cytocompatibility (>95% viability). The highly pure radiolabeled conjugate (99.68%) also remained stable, exceeding 95% over one physical half-life and retaining 80-85% stability at 48 hours in PBS and serum. In vivo studies revealed specific tumor uptake (0.87 ± 0.19 %ID/g), which decreased by 31% after L-arginine blocking (p < 0.05). SPECT imaging demonstrated a strong early tumor uptake (SUVmax 4.8 at 30 min) with rapid blood clearance, while kinetic modeling indicated fast tumor influx, efficient irreversible trapping, and minimal efflux.
Conclusion: ⁹⁹ᵐTc-DND-G2-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.
Keywords
Technetium
Dendrimers
Arginine
Radionuclide Imaging
Breast Neoplasms
Subjects
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Available Online from 22 September 2026