Development of 177Lu-Cetuximab-PAMAM dendrimeric nanosystem: a novel theranostic radioimmunoconjugate

Hosseini, Seyed Mohammad; Mohammadnejad, Javad; Yousefnia, Hassan; Alirezapour, Behrouz; Rezayan, Ali Hossein

doi:10.1007/s00432-023-04724-z

Cited by 2 publications

(1 citation statement)

References 57 publications

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“…Hosseini et al ( 2023 ) modified G4 PAMAM dendrimers with cetuximab for targeting EGFR and CHX-diethylenetriaminepentaacetic acid (CHX-DTPA) to complex 177 Lu. G4 PAMAM dendrimers were relatively non-cytotoxic to EGFR-positive SW-480 human colon cancer cells in vitro, but conjugation of dendrimers to cetuxumab and especially, labeling with 177 Lu increased cytotoxic potency.…”

Section: Main Textmentioning

confidence: 99%

Radiation nanomedicines for cancer treatment: a scientific journey and view of the landscape

Reilly,

Georgiou,

Brown

et al. 2024

EJNMMI radiopharm. chem.

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Background Radiation nanomedicines are nanoparticles labeled with radionuclides that emit α- or β-particles or Auger electrons for cancer treatment. We describe here our 15 years scientific journey studying locally-administered radiation nanomedicines for cancer treatment. We further present a view of the radiation nanomedicine landscape by reviewing research reported by other groups. Main body Gold nanoparticles were studied initially for radiosensitization of breast cancer to X-radiation therapy. These nanoparticles were labeled with 111In to assess their biodistribution after intratumoural vs. intravenous injection. Intravenous injection was limited by high liver and spleen uptake and low tumour uptake, while intratumoural injection provided high tumour uptake but low normal tissue uptake. Further, [111In]In-labeled gold nanoparticles modified with trastuzumab and injected iintratumourally exhibited strong tumour growth inhibition in mice with subcutaneous HER2-positive human breast cancer xenografts. In subsequent studies, strong tumour growth inhibition in mice was achieved without normal tissue toxicity in mice with human breast cancer xenografts injected intratumourally with gold nanoparticles labeled with β-particle emitting 177Lu and modified with panitumumab or trastuzumab to specifically bind EGFR or HER2, respectively. A nanoparticle depot (nanodepot) was designed to incorporate and deliver radiolabeled gold nanoparticles to tumours using brachytherapy needle insertion techniques. Treatment of mice with s.c. 4T1 murine mammary carcinoma tumours with a nanodepot incorporating [90Y]Y-labeled gold nanoparticles inserted into one tumour arrested tumour growth and caused an abscopal growth-inhibitory effect on a distant second tumour. Convection-enhanced delivery of [177Lu]Lu-AuNPs to orthotopic human glioblastoma multiforme (GBM) tumours in mice arrested tumour growth without normal tissue toxicity. Other groups have explored radiation nanomedicines for cancer treatment in preclinical animal tumour xenograft models using gold nanoparticles, liposomes, block copolymer micelles, dendrimers, carbon nanotubes, cellulose nanocrystals or iron oxide nanoparticles. These nanoparticles were labeled with radionuclides emitting Auger electrons (111In, 99mTc, 125I, 103Pd, 193mPt, 195mPt), β-particles (177Lu, 186Re, 188Re, 90Y, 198Au, 131I) or α-particles (225Ac, 213Bi, 212Pb, 211At, 223Ra). These studies employed intravenous or intratumoural injection or convection enhanced delivery. Local administration of these radiation nanomedicines was most effective and minimized normal tissue toxicity. Conclusions Radiation nanomedicines have shown great promise for treating cancer in preclinical studies. Local intratumoural administration avoids sequestration by the liver and spleen and is most effective for treating tumours, while minimizing normal tissue toxicity.

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Section: Main Textmentioning

confidence: 99%

Radiation nanomedicines for cancer treatment: a scientific journey and view of the landscape

Reilly,

Georgiou,

Brown

et al. 2024

EJNMMI radiopharm. chem.

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New Approaches in Gastric Cancer Immunotherapy

Mousavi,

Ahmadi,

Behzadifar

et al. 2024

Gastric Cancer - Progress and Challenges in the Era of Precision Medicine [Working Title]

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Cancer has an inferior prognosis in most cases and is often challenging to treat. Gastric cancer (GC), which is among leading causes of the top five malignant tumor deaths worldwide and whose incidence is increasing every day, is no exception. GC is frequently diagnosed at a progressive or metastatic stage of the disease. At this stage, the clinical effectiveness of conventional treatments such as surgery and chemotherapy is limited, and the median overall survival is reduced to only about a few months. The tumor microenvironment (TME) and the specific conditions that govern it, concurrently with multiple mutations, have significantly increased the resistance of cancer cells. However, the study of molecular biology, cell signaling pathways, and immune system function provides a new approach using immunotherapy such as immune inhibitors, T cell transfer therapy, monoclonal antibodies (mAbs), therapeutic vaccines, etc. to overcome cancer resistance. In addition, the use of nanoparticles (NPs), especially theranostic NPs permits for better monitoring of the response during treatment, and its combination with immunotherapy, promising strategies for providing a new treatment. This chapter provides an overview of these new advances in treating GC cancer.

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Development of 177Lu-Cetuximab-PAMAM dendrimeric nanosystem: a novel theranostic radioimmunoconjugate

Cited by 2 publications

References 57 publications

Radiation nanomedicines for cancer treatment: a scientific journey and view of the landscape

Radiation nanomedicines for cancer treatment: a scientific journey and view of the landscape

New Approaches in Gastric Cancer Immunotherapy

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