Journal of Nuclear Medicine | Application of CD70-Targeted PET Imaging in Burkitt Lymphoma

This study introduces a novel 44Sc-labeled single-domain antibody fragment, [44Sc]Sc-CHX-A99-DTPA-RCCB6, for CD70-targeted immunoPET imaging. The tracer demonstrates excellent stability, specificity, and imaging performance in Burkitt lymphoma models, providing a strong foundation for clinical translation.

 

Literature Overview
This article, "[44Sc]Sc-CHX-A99-DTPA-RCCB6: A PET Tracer for Imaging CD70 Expression Across Latency Types of Burkitt Lymphoma", published in the Journal of Nuclear Medicine, reviews CD70 as an imaging target for Burkitt lymphoma (BL). The research team developed a 44Sc-labeled single-domain antibody fragment and systematically evaluated its imaging performance in BL models with different latency types. The article highlights the tracer's potential for differentiating CD70 expression levels and improving tumor-to-background contrast, while emphasizing its clinical translational significance.

Background Knowledge
CD70 is a type II transmembrane protein acting as a ligand for CD27. It is highly expressed in Burkitt lymphoma (BL), particularly in type III latency models, and is closely associated with immune escape and disease progression. BL is an aggressive B-cell non-Hodgkin lymphoma characterized by rapid progression and distinct genetic features, making early diagnosis critical for improving patient outcomes. While conventional [18F]FDG PET imaging is widely used clinically, its lack of target specificity often leads to false-positive results. Developing CD70-targeted PET tracers thus represents a key direction for enhancing diagnostic accuracy. 44Sc, a radioactive metal with a longer half-life and high positron emission efficiency, better matches the pharmacokinetics of single-domain antibodies. Its isotope pair (44Sc/47Sc) further enables theranostic applications. Although partial studies on 68Ga or 64Cu-labeled CD70 tracers exist, this work is the first systematic evaluation of 44Sc-labeled RCCB6 in BL models, filling a critical gap in CD70-targeted imaging for BL. The team also employed the Cre-LoxP system to construct latency-type BL models, assessing tracer specificity across different latency phases and validating CD70 as a molecular imaging target.

 

 

Research Methods and Experiments
The research team conjugated the RCCB6 single-domain antibody with CHX-A99-DTPA and radiolabeled it with 44Sc to produce a stable tracer [44Sc]Sc-CHX-A99-DTPA-RCCB6. In vitro stability, cell uptake, binding, and internalization experiments were conducted using Burkitt lymphoma cell lines (type III and type I latency) to evaluate CD70 specificity. In vivo stability was assessed in NSG mouse models through PET imaging and biodistribution studies. Near-infrared fluorescence (NIRF) imaging validated tracer accumulation at tumor sites, while immunohistochemistry confirmed CD70 expression levels.

Key Conclusions and Perspectives

• The 44Sc-labeled RCCB6 tracer demonstrated high radiolabeling yield and excellent stability both in vitro and in vivo, supporting its suitability as an immunoPET imaging agent.
• Significant tracer binding and internalization were observed in CD70-positive type III latency BL cells, whereas minimal binding occurred in CD70-negative type I latency cells, confirming its specificity.
• Competitive binding experiments revealed IC50 values of 16.45 ± 2.82 nM for RCCB6 and 38.74 ± 4.66 nM for CHX-A99-RCCB6, indicating comparable binding affinity.
• Saturation binding experiments determined a maximum binding capacity of 4.83 ± 0.52 pM with a receptor density of 2.36 ± 0.26 × 106 receptors/cell in type III latency BL cells, further validating target specificity.
• PET imaging and biodistribution studies showed substantial tracer accumulation in type III latency BL tumors, maintaining high tumor uptake (2.85 ± 0.84 %ID/g) even 6 hours post-injection, while minimal accumulation was observed in type I latency tumors and blocked groups (0.35 ± 0.03 %ID/g and 0.58 ± 0.16 %ID/g, respectively).
• NIRF imaging confirmed tracer accumulation in type III latency BL tumors, and immunohistochemistry demonstrated significantly higher CD70 expression in type III latency BL tissues compared to type I.

Research Significance and Prospects
This study provides experimental evidence supporting clinical translation of CD70-targeted PET imaging in Burkitt lymphoma. Given the pronounced CD70 expression in type III latency BL, the tracer holds promise for patient stratification, treatment monitoring, and precision medicine applications. Future research should focus on optimizing renal clearance properties to enhance safety. Additionally, multimodal strategies combining NIRF and PET imaging may improve tumor detection sensitivity and tracer evaluation accuracy, offering new directions for CD70-targeted imaging studies.

 

 

Conclusion
[44Sc]Sc-CHX-A99-DTPA-RCCB6 demonstrates high specificity in Burkitt lymphoma models, effectively distinguishing CD70 expression across latency types. The tracer exhibits robust stability in vitro and in vivo, enabling rapid tumor uptake and sustained retention in type III latency BL models. Although renal clearance is the primary elimination pathway, minimal uptake in non-target organs ensures favorable tumor-to-background contrast. NIRF and immunohistochemical imaging further validate the tracer's targeting capability. The study highlights its translational potential in preclinical settings, supporting applications in CD70-targeted diagnostics and treatment monitoring. Future work should address optimizing renal clearance, enhancing imaging resolution, and advancing clinical trials to validate safety and efficacy in human patients. This research provides a new molecular imaging tool for Burkitt lymphoma and establishes a foundation for precision evaluation of CD70-targeted therapies.

 

Xiaoyan Li, Yajie Zhao, Jessica C Hsu, Shuo Hu, and Weibo Cai. [44Sc]Sc-CHX-A″-DTPA-RCCB6: A PET Tracer for Imaging CD70 Expression Across Latency Types of Burkitt Lymphoma. Journal of Nuclear Medicine.