Abstract
Simple SummaryBeyond its pre-eminent role in the context of tumor cell growth as well as metastasis, the C-X-C motif chemokine receptor 4 (CXCR4) is a key player in the orchestration of inflammatory responses to inflammatory stimuli. This review therefore particularly focuses on summarizing the current knowledge on non-invasive imaging of tissue infiltration with CXCR4-expressing immune cells in the context of diverse inflammatory conditions using positron emission tomography. An overview of the current clinical and preclinical approaches in this context is provided, and the recent advances in the development of dedicated, high-end CXCR4-targeted imaging tools and theranostic agents are discussed.Given its pre-eminent role in the context of tumor cell growth as well as metastasis, the C-X-C motif chemokine receptor 4 (CXCR4) has attracted a lot of interest in the field of nuclear oncology, and clinical evidence on the high potential of CXCR4-targeted theranostics is constantly accumulating. Additionally, since CXCR4 also represents a key player in the orchestration of inflammatory responses to inflammatory stimuli, based on its expression on a variety of pro- and anti-inflammatory immune cells (e.g., macrophages and T-cells), CXCR4-targeted inflammation imaging has recently gained considerable attention. Therefore, after briefly summarizing the current clinical status quo of CXCR4-targeted theranostics in cancer, this review primarily focuses on imaging of a broad spectrum of inflammatory diseases via the quantification of tissue infiltration with CXCR4-expressing immune cells. An up-to-date overview of the ongoing preclinical and clinical efforts to visualize inflammation and its resolution over time is provided, and the predictive value of the CXCR4-associated imaging signal for disease outcome is discussed. Since the sensitivity and specificity of CXCR4-targeted immune cell imaging greatly relies on the availability of suitable, tailored imaging probes, recent developments in the field of CXCR4-targeted imaging agents for various applications are also addressed.
Highlights
In inflammation imaging, the current first “proof-of-concept” data in patients need to be further validated in prospective clinical trials
The existing data clearly show the high potential of this approach for visualizing inflammation and its resolution over time in a broad spectrum of inflammatory diseases
C-X-C motif chemokine receptor 4 (CXCR4)-targeted imaging may serve as a tool for non-invasive therapy control after anti-inflammatory treatments and for providing personalized anti-inflammatory treatments to improve disease outcome
Summary
Given its pre-eminent role in the context of tumor cell growth as well as metastasis, the C-X-C motif chemokine receptor 4 (CXCR4) has attracted a lot of interest in nuclear oncology. Powerful imaging agents and a theranostic concept targeting CXCR4 have evolved during the last decade, and their increasing clinical impact is reflected by an elevenfold increase in the number of publications per year Imaging inflammation (i.e., infiltration of tissues by CXCR4-expressing immune cells) by targeting CXCR4 has become another very vibrant field of preclinical and clinical research. After a short summary of the recent clinical advances in CXCR4-targeted imaging and radioligand therapy (RLT) in cancer, this review will highlight the increasing body of evidence of the clinically relevant role of CXCR4 imaging in the context of inflammatory conditions. Important recent findings in preclinical studies in this field as well as the very recent developments of innovative and promising new tracer concepts will be addressed
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