Abstract
Purpose
Epidermal growth factor receptors (EGFRs) are overexpressed in a wide range of tumors and are attractive candidates to target in targeted therapies. This study aimed to introduce a novel radiolabeled compound, 177Lu-cetuximab-PAMAM G4, for the treatment of EGFR-expressing tumors.
Methods
In this study, the cetuximab mAb was bound to PAMAM G4 and labeled with 177Lu via DTPA-CHX chelator. The synthesized nanosystem was confirmed by different analyses such as DLS, FT-IR, TEM, and RT-LC. Cell viability of the radioimmunoconjugate was assessed over the EGFR-expressing cell line of SW480. The biodistribution of 177Lu-Cetuximab-PAMAMG4 was determined in different intervals after injection of the radiolabeled compound in normal and tumoral nude mice via scarification and SPECT images.
Results
The average size of PAMAM G4 and PAMAM-Cetuximab-DTPA-CHX nanoparticles were 2 and 70 nm, respectively. 177Lu-Cetuximab-PAMAMG4 was prepared with radiochemical purity of more than 98%. The survival rates of SW480 cells at 24, 48, and 72 h post-treatment with177Lu-Cetuximab-PAMAMG4 (500 nM) were 18%, 15%, and 14%, respectively. The biodistribution studies showed a significant accumulation of 177Lu-Cetuximab-PAMAM in the EGFR-expressing tumor.
Conclusion
According to the results, this new agent can be considered as an efficient therapeutic complex for tumors expressing EGFR receptors.
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Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- AB:
-
Antibodies
- TGF-α:
-
Alpha-transforming growth factor
- CHO:
-
Chinese hamster ovary cell
- DMSO:
-
Dimethyl sulfoxide
- DLS:
-
Dynamic light scattering
- DTPA:
-
Diethylenetriamine pentaacetate
- EDC:
-
N-(3-Dimethylaminopropyl)-N′-ethyl carbodiimide hydrochloride
- EDTA:
-
Ethylenediaminetetraacetic acid
- EGFR:
-
Epidermal growth factor receptor
- ELISA:
-
Enzyme-linked immunosorbent assay
- FBS:
-
Fetal bovine serum
- FESEM:
-
Field emission scanning electron microscope
- FTIR:
-
Fourier transform infrared spectroscopy
- HNSCC:
-
Head and neck squamous cell carcinoma
- HPGe:
-
High purity germanium
- ID/g:
-
Injected dose per gram
- mCRC:
-
Metastatic colorectal cancer
- mAb:
-
Monoclonal antibody
- MRI:
-
Magnetic resonance imaging
- MTT:
-
3-[4,5-Dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide
- NHS:
-
N-hydroxysuccinimide
- NPs:
-
NanoParticles
- PAMAM G4:
-
Polyamidoamine dendrimer generation 4
- PBS:
-
Phosphate buffered saline
- RTLC:
-
Radio thin-layer chromatography
- SPECT:
-
Single photon emission computed tomography
- TEM:
-
Transmission electron microscopy
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This study was extracted from an MSc thesis. The authors would like to acknowledge for all the support of NSTRI and the University of Tehran.
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This work was supported by Nuclear Science and Technology Research Institute.
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Hosseini, S.M., Mohammadnejad, J., Yousefnia, H. et al. Development of 177Lu-Cetuximab-PAMAM dendrimeric nanosystem: a novel theranostic radioimmunoconjugate. J Cancer Res Clin Oncol 149, 7779–7791 (2023). https://doi.org/10.1007/s00432-023-04724-z
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DOI: https://doi.org/10.1007/s00432-023-04724-z