In Vivo Targeting of CXCR4—New Horizons

Abstract

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.

CXCR4 peptide-based fluorescence endoscopy in a mouse model of Barrett’s esophagus

“…Indeed, the murine CXCR4 has limited homology with human CXCR4 and a modification of MK007 for human CXCR4 may be needed. Nevertheless, our data from in vitro studies and first clinical data on a patient with multiple myeloma (MM) using a new CXCR4-targeted Tc ligand ( 99m Tc; based on the structure of MK007) for SPECT/CT imaging [ 34 ] are encouraging for the potential clinical use of a modified MK007. Indeed, the ligand accumulated in intramedullary MM lesions and no high accumulation was observed in the liver, in contrast to mice [ 34 ].…”

“…Nevertheless, our data from in vitro studies and first clinical data on a patient with multiple myeloma (MM) using a new CXCR4-targeted Tc ligand ( 99m Tc; based on the structure of MK007) for SPECT/CT imaging [ 34 ] are encouraging for the potential clinical use of a modified MK007. Indeed, the ligand accumulated in intramedullary MM lesions and no high accumulation was observed in the liver, in contrast to mice [ 34 ]. Furthermore, we have not yet determined the affinity of MK007 for the murine CXCR4 receptor and the specificity of MK007 in the IL1B model.…”

Diagnostic Value, Prognostic Value, and Immune Infiltration of LOX Family Members in Liver Cancer: Bioinformatic Analysis

“…Apart from the above immunostimulators, the CXCR4 was associated with both LOX and LOXL3. It is expressed on various pro-and anti-inflammatory immune cells, especially in macrophages and T cells (101). Multiple drugs targeted on CXCR4 have been under investigation (102).…”

Imaging Aldosterone-Producing Adrenocortical Carcinoma With 68Ga-Pentixafor PET/CT

“…6 Therefore, in vivo quantification of CXCR4 expression using CXCR4-targeted PET/CT imaging has received some consideration. [7][8][9] Recently, a growing literature has reported that 68 Ga-pentixafor PET/CT plays an important role in the diagnosis of some tumors and inflammation. [10][11][12] It has now been demonstrated that the high expression of CXCR4 in aldosterone-producing adrenal tumors is closely associated with the expression of CYP11B2 (aldosterone synthase).…”

“…CXCR4 is expressed by a variety of inflammatory and malignant cells 6 . Therefore, in vivo quantification of CXCR4 expression using CXCR4-targeted PET/CT imaging has received some consideration 7–9 . Recently, a growing literature has reported that 68 Ga-pentixafor PET/CT plays an important role in the diagnosis of some tumors and inflammation 10–12 .…”