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Radiolabelling and preclinical characterisation of [89Zr]Zr-Df-ATG-101 bispecific to PD-L1/4-1BB.
Cao, Zhipeng; Wichmann, Christian Werner; Burvenich, Ingrid Julienne Georgette; Osellame, Laura Danielle; Guo, Nancy; Rigopoulos, Angela; O'Keefe, Graeme Joseph; Scott, Fiona Elizabeth; Lorensuhewa, Nirmal; Lynch, Kevin Patrick; Scott, Andrew Mark.
Afiliación
  • Cao Z; Tumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, Melbourne, Australia.
  • Wichmann CW; School of Cancer Medicine, La Trobe University, Melbourne, Australia.
  • Burvenich IJG; Department of Molecular Imaging and Therapy, Austin Health, Melbourne, Australia.
  • Osellame LD; Tumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, Melbourne, Australia.
  • Guo N; School of Cancer Medicine, La Trobe University, Melbourne, Australia.
  • Rigopoulos A; Department of Molecular Imaging and Therapy, Austin Health, Melbourne, Australia.
  • O'Keefe GJ; School of Chemistry - Bio21 Institute, University of Melbourne, Melbourne, Australia.
  • Scott FE; Tumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, Melbourne, Australia.
  • Lorensuhewa N; School of Cancer Medicine, La Trobe University, Melbourne, Australia.
  • Lynch KP; Tumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, Melbourne, Australia.
  • Scott AM; School of Cancer Medicine, La Trobe University, Melbourne, Australia.
Eur J Nucl Med Mol Imaging ; 51(11): 3202-3214, 2024 Sep.
Article en En | MEDLINE | ID: mdl-38730087
ABSTRACT

PURPOSE:

ATG-101, a bispecific antibody that simultaneously targets the immune checkpoint PD-L1 and the costimulatory receptor 4-1BB, activates exhausted T cells upon PD-L1 crosslinking. Previous studies demonstrated promising anti-tumour efficacy of ATG-101 in preclinical models. Here, we labelled ATG-101 with 89Zr to confirm its tumour targeting effect and tissue biodistribution in a preclinical model. We also evaluated the use of immuno-PET to study tumour uptake of ATG-101 in vivo.

METHODS:

ATG-101, anti-PD-L1, and an isotype control were conjugated with p-SCN-Deferoxamine (Df). The Df-conjugated antibodies were radiolabelled with 89Zr, and their radiochemical purity, immunoreactivity, and serum stability were assessed. We conducted PET/MRI and biodistribution studies on [89Zr]Zr-Df-ATG-101 in BALB/c nude mice bearing PD-L1-expressing MDA-MB-231 breast cancer xenografts for up to 10 days after intravenous administration of [89Zr]Zr-labelled antibodies. The specificity of [89Zr]Zr-Df-ATG-101 was evaluated through a competition study with unlabelled ATG-101 and anti-PD-L1 antibodies.

RESULTS:

The Df-conjugation and [89Zr]Zr -radiolabelling did not affect the target binding of ATG-101. Biodistribution and imaging studies demonstrated biological similarity of [89Zr]Zr-Df-ATG-101 and [89Zr]Zr-Df-anti-PD-L1. Tumour uptake of [89Zr]Zr-Df-ATG-101 was clearly visualised using small-animal PET imaging up to 7 days post-injection. Competition studies confirmed the specificity of PD-L1 targeting in vivo.

CONCLUSION:

[89Zr]Zr-Df-ATG-101 in vivo distribution is dependent on PD-L1 expression in the MDA-MB-231 xenograft model. Immuno-PET with [89Zr]Zr-Df-ATG-101 provides real-time information about ATG-101 distribution and tumour uptake in vivo. Our data support the use of [89Zr]Zr-Df-ATG-101 to assess tumour and tissue uptake of ATG-101.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Circonio / Anticuerpos Biespecíficos / Antígeno B7-H1 Límite: Animals / Female / Humans Idioma: En Revista: Eur J Nucl Med Mol Imaging Asunto de la revista: MEDICINA NUCLEAR Año: 2024 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Circonio / Anticuerpos Biespecíficos / Antígeno B7-H1 Límite: Animals / Female / Humans Idioma: En Revista: Eur J Nucl Med Mol Imaging Asunto de la revista: MEDICINA NUCLEAR Año: 2024 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Alemania