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Preclinical Comparison of [In]In- and [Ac]Ac-DOTA-Trastuzumab IgG, F(ab') and Fab for Theranostic SPECT/CT Imaging and α-Particle Radioimmunotherapy of HER2-Positive Human Breast Cancer.
Mol 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 PDFTargeted radionuclide therapy against GARP expressing T regulatory cells after tumour priming with external beam radiotherapy in a murine syngeneic model.
Heliyon
October 2024
Centre George-François Leclerc, Service de Médecine Nucléaire, IMATHERA UMS INSERM BioSanD US58, 1 rue du Professeur Marion, 21079, Dijon, France.
Purpose: Radiation therapy (RT) exerts its anti-tumour efficacy by inducing direct damage to cancer cells but also through modification of the tumour microenvironment (TME) by inducing immunogenic antitumor response. Conversely, RT also promotes an immunosuppressive TME notably through the recruitment of regulatory T cells (Tregs). Glycoprotein A repetitions predominant (GARP), a transmembrane protein highly expressed by activated Tregs, plays a key role in the activation of TGF-β and thus promotes the immunosuppressive action of Tregs.
View Article and Find Full Text PDFPARP-Targeted Radiotheranostics with Auger Electrons: An Updated Overview.
Curr Issues Mol Biol
March 2024
Department of Biomedical Sciences, Humanitas University, 20072 Milan, Italy.
Auger electrons (AEs) represent an intriguing topic in the field of radionuclide therapy. They are emitted by several radionuclides commonly used in nuclear medicine (indium-111, iodine-123, iodine-125), allowing for highly localized energy deposition and thus exerting a radiotoxic effect on specific cellular and sub-cellular targets. However, due to their short range in matter, AEs have had limited use in therapeutic applications so far.
View Article and Find Full Text PDFOptimized, automated and cGMP-compliant synthesis of the HER2 targeting [Ga]Ga-ABY-025 tracer.
EJNMMI Radiopharm Chem
November 2023
Department of Radiopharmacy, Karolinska University Hospital, 171 76, Stockholm, Sweden.
Background: The Affibody molecule, ABY-025, has demonstrated utility to detect human epidermal growth factor receptor 2 (HER2) in vivo, either radiolabelled with indium-111 (In) or gallium-68 (Ga). Using the latter, Ga, is preferred due to its use in positron emission tomography with superior resolution and quantifying capabilities in the clinical setting compared to In. For an ongoing phase II study (NCT05619016) evaluating ABY-025 for detecting HER2-low lesions and selection of patients for HER2-targeted treatment, the aim was to optimize an automated and cGMP-compliant radiosynthesis of [Ga]Ga-ABY-025.
View Article and Find Full Text PDFAdjuvant Auger Electron-Emitting Radioimmunotherapy with [In]In-DOTA-Panitumumab in a Mouse Model of Local Recurrence and Metastatic Progression of Human Triple-Negative Breast Cancer.
Mol Pharm
December 2023
Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College St., Toronto, Ontario M5S 3M2, Canada.
Triple-negative breast cancer (TNBC) has a high risk for recurrence and metastasis. We studied the effectiveness of Auger electron (AE) radioimmunotherapy (RIT) with antiepidermal growth factor receptor (EGFR) panitumumab conjugated with DOTA complexed to In ([In]In-DOTA-panitumumab) for preventing metastatic progression after local treatment of 231/LM2-4 Luc+ human TNBC tumors in the mammary fat pad of NRG mice. Prior to RIT, the primary tumor was resected, and tumor margins were treated with X-irradiation (XRT; 5 days × 6 Gy/d).
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