Dataset Information

⁶⁴Cu-labeled daratumumab F(ab')₂ fragment enables early visualization of CD38-positive lymphoma.

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.

SUBMITTER: Kang L

PROVIDER: S-EPMC8940612 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

<sup>64</sup>Cu-labeled daratumumab F(ab')<sub>2</sub> fragment enables early visualization of CD38-positive lymphoma.

Kang Lei L Li Cuicui C Yang Qi Q Sutherlin Logan L Wang Lin L Chen Zhao Z Becker Kaelyn V KV Huo Nan N Qiu Yongkang Y Engle Jonathan W JW Wang Rongfu R He Chengzhi C Jiang Dawei D Xu Xiaojie X Cai Weibo W

European journal of nuclear medicine and molecular imaging 20211022 5

<h4>Purpose</h4>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 <sup>64</sup>Cu-labeled Dara-F(ab')<sub>2</sub> for the visualiz ...[more]

PMID: 34677626

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Dataset Information

⁶⁴Cu-labeled daratumumab F(ab')₂ fragment enables early visualization of CD38-positive lymphoma.

Purpose

Methods

Results

Conclusions

Publications

<sup>64</sup>Cu-labeled daratumumab F(ab')<sub>2</sub> fragment enables early visualization of CD38-positive lymphoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

64Cu-labeled daratumumab F(ab')2 fragment enables early visualization of CD38-positive lymphoma.

Purpose

Methods

Results

Conclusions

Publications

<sup>64</sup>Cu-labeled daratumumab F(ab')<sub>2</sub> fragment enables early visualization of CD38-positive lymphoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

⁶⁴Cu-labeled daratumumab F(ab')₂ fragment enables early visualization of CD38-positive lymphoma.