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64Cu-labeled daratumumab F(ab′)2 fragment enables early visualization of CD38-positive lymphoma.
- Source :
-
European Journal of Nuclear Medicine & Molecular Imaging . Apr2022, Vol. 49 Issue 5, p1470-1481. 12p. 1 Color Photograph, 1 Diagram, 4 Graphs. - Publication Year :
- 2022
-
Abstract
- Purpose: Abnormal CD38 expression in some hematologic malignancies, including lymphoma, has made it a biomarker for targeted therapies. Daratumumab (Dara) is the first FDA-approved CD38-specific monoclonal antibody, enabling successfully immunoPET imaging over the past years. Radiolabeled Dara however has a long blood circulation and delayed tumor uptake which can limit its applications. The focus of this study is to develop 64Cu-labeled Dara-F(ab′)2 for the visualization of CD38 in lymphoma models. Methods: F(ab′)2 fragment was prepared from Dara using an IdeS enzyme and purified with Protein A beads. Western blotting, flow cytometry, and surface plasmon resonance (SPR) were performed for in vitro assay. Probes were labeled with 64Cu after the chelation of 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). Small animal PET imaging and quantitative analysis were performed after injection of 64Cu-labeled Dara-F(ab′)2, IgG-F(ab′)2, and Dara for evaluation in lymphoma models. Results: Flow cytometry and SPR assay proved the specific binding ability of Dara-F(ab′)2 and NOTA-Dara-F(ab′)2 in vitro. Radiolabeling yield of [64Cu]Cu-NOTA-Dara-F(ab′)2 was over 90% and with a specific activity of 4.0 ± 0.6 × 103 MBq/μmol (n = 5). PET imaging showed [64Cu]Cu-NOTA-Dara-F(ab′)2 had a rapid and high tumor uptake as early as 2 h (6.9 ± 1.2%ID/g) and peaked (9.5 ± 0.7%ID/g) at 12 h, whereas [64Cu]Cu-NOTA-Dara reached its tumor uptake peaked at 48 h (8.3 ± 1.4%ID/g, n = 4). In comparison, IgG-F(ab′)2 and HBL-1 control groups found no noticeable tumor uptake. [64Cu]Cu-NOTA-Dara-F(ab′)2 had significantly lower uptake in blood pool, bone, and muscle than [64Cu]Cu-NOTA-Dara and its tumor-to-blood and tumor-to-muscle ratios were significantly higher than controls. Conclusions: [64Cu]Cu-NOTA-Dara-F(ab′)2 showed a rapid and high tumor uptake in CD38-positive lymphoma models with favorable imaging contrast, showing its promise as a potential PET imaging agent for future clinical applications. [ABSTRACT FROM AUTHOR]
- Subjects :
- *FLOW cytometry
*IN vitro studies
*BIOLOGICAL models
*CHELATION therapy
*ANIMAL experimentation
*WESTERN immunoblotting
*MONOCLONAL antibodies
*QUANTITATIVE research
*GENE expression
*RADIOPHARMACEUTICALS
*POSITRON emission tomography
*DESCRIPTIVE statistics
*COPPER
*DRUG development
*LYMPHOMAS
*TUMOR markers
*SURFACE plasmon resonance
Subjects
Details
- Language :
- English
- ISSN :
- 16197070
- Volume :
- 49
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- European Journal of Nuclear Medicine & Molecular Imaging
- Publication Type :
- Academic Journal
- Accession number :
- 155912908
- Full Text :
- https://doi.org/10.1007/s00259-021-05593-9