Aim: PR81 is a monoclonal antibody that binds with high affinity to MUC1 antigen that is over expressed in 80% of breast cancers. In this study, we developed a method for indirect labeling of PR81 with lutetium-177 and performed all preclinical qualifications in production of a biologic agent for radioimmunotherapy of breast cancer.
Materials And Methods: The radiochemical purity and in vitro stability of (177)Lu labeled PR81 was determined by instant thin layer chromatography. The immunoreactivity and cell toxicity of the complex were tested on MCF7 cell line. The biodistribution and scintigraphy studies were performed in BALB/c mice with breast tumor.
Results: The radiochemical purity was 91.2±3.8% after 2 h. The in vitro stabilities in phosphate buffer and human blood serum were 83.1±3.4% and 76.2±3.6% at 96 h, respectively. The immunoreactivity of the complex was 83.4±2.4%. The cell toxicity study showed that the complex inhibited 85.2±3.4% growth of MCF7 cells at a concentration of 2500 ng/ml after 96 h. The biodistribution and scintigraphy studies showed the accumulation of the complex at the site of tumors with high sensitivity and specificity.
Conclusion: The results showed that one may consider (177)Lu-DOTA-PR81 as a potential radiopharmaceutical for therapy of human breast cancer, which needs further investigations.
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http://dx.doi.org/10.1016/j.nucmedbio.2011.02.009 | DOI Listing |
Biomaterials
May 2025
Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China. Electronic address:
Radiotherapy (RT) induced abscopal effect has garnered substantial attention, nevertheless, it is rarely observed in clinics, due to the tumor hypoxia-related radioresistance, inadequate immune stimulation, and immunosuppressive tumor microenvironment. Herein, we construct a radiotherapy-immunomodulated nanoplatform (THUNDER), which synergizes with RT and greatly triggers the generation of both hypoxic and normoxic tumor cells-derived tumor-associated antigens (TAAs), resulting in robust abscopal effect and sustained immune memory. THUNDER exhibits prolonged blood circulation and high tumor retention capacity.
View Article and Find Full Text PDFMol Pharm
January 2025
Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON M5S 3M2, Canada.
Radioimmunotherapy (RIT) with α-particle-emitting, Ac complexed to trastuzumab may offer an alternative treatment for patients who progress on HER2-targeted therapies. Moreover, RIT with [Ac]Ac-DOTA-trastuzumab could be combined with SPECT/CT imaging with [In]In-DOTA-trastuzumab in a theranostic approach. In this study, we compared DOTA-conjugated trastuzumab IgG, F(ab') or Fab complexed to In or Ac for SPECT/CT imaging and α-particle RIT of subcutaneous (s.
View Article and Find Full Text PDFJ Nanobiotechnology
November 2024
Guangdong Provincial Key Laboratory of New Drug Screening, Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, P.R. China.
Radiotherapy (RT) stands as a frontline treatment modality in clinical breast oncology, yet challenges like ROS reduction, high toxicity, non-selectivity, and hypoxia hinder efficacy. Additionally, RT administered at different doses can induce varying degrees of radioimmunotherapy. High doses of radiation (>10 Gy) may result in immune suppression, while moderate doses (4-10 Gy), although capable of mitigating the immune suppression caused by high-dose radiation, are often insufficient in effectively killing tumor cells.
View Article and Find Full Text PDFJ Control Release
December 2024
School of Pharmacy, Institute of Aging Medicine, Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, Binzhou Medical University, Yantai 264003, PR China. Electronic address:
Radiotherapy (RT)-mediated immune activation is insufficient for effective therapy of triple-negative breast cancer (TNBC) due to the immunosuppressive tumor microenvironment. Herein, we developed an oxygen self-supplying nanoradiosensitizer to activate immunogenic cell death (ICD) and the cGAS-STING signaling pathway, elevating the anti-tumor immune response and improving radioimmunotherapy for TNBC. The nanoradiosensitizer was fabricated using astragaloside liposome-encapsulated FePt alloy and MnO nanocrystals (ALFM).
View Article and Find Full Text PDFACS Appl Mater Interfaces
October 2024
The Yancheng School of Clinical Medicine of Nanjing Medical University, Yancheng Third People's Hospital, Yancheng, Jiangsu 224001, China.
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