PET Imaging Radiotracers of Chemokine Receptors

Alluri, Santosh Reddy; Higashi, Yusuke; Kil, Kun-Eek

doi:10.3390/molecules26175174

Cited by 10 publications

(5 citation statements)

References 158 publications

(165 reference statements)

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“…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).…”

Section: Figurementioning

confidence: 99%

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

et al. 2022

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Chemokine receptor 4 (CXCR4) is a 7-transmembrane G protein-coupled receptor, and pentixafor is considered to be a potent ligand for the CXCR4 receptor. Recently, 68 Ga-pentixafor has been reported as a potential PET imaging agent for CXCR4-positive tumors and inflammatory lesions, including adrenocortical lesions. We report a case of primary aldosteronism due to adrenocortical carcinoma with intense 68 Ga-pentixafor activity on PET/CT.

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Section: Figurementioning

confidence: 99%

“…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 .…”

mentioning

confidence: 99%

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

et al. 2022

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“…Based on the identification of the first highly potent, synthetic CXCR4-targeted anti-HIV antagonists in the late 1990s [ 89 , 90 ], and fueled by the recognition of the important role of CXCR4 in cancer growth, progression and metastasis in the early 2000s [ 91 ], the development of CXCR4-targeted imaging agents has been a field of highly active research since the mid-2000s ( Figure 2 ). Several excellent reviews on the progressive advances in the design of CXCR4-directed nuclear, fluorescent and hybrid imaging agents have been published over the years [ 1 , 3 , 92 , 93 , 94 ]. Since they already provide an impressive and comprehensive overview of the historical evolution of the different tracer concepts (summarized in Figure 2 ), only very recent (2019 and later) advances and developments will be discussed in this review.…”

Section: Cxcr4-targeted Imaging Agents: An Ever-evolving Fieldmentioning

confidence: 99%

“…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 eleven-fold increase in the number of publications per year (PubMed search for “CXCR4 imaging PET cancer”) during the last decade (2011–2020) and highlighted in several comprehensive reviews [ 1 , 2 , 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

In Vivo Targeting of CXCR4—New Horizons

Schottelius

Herrmann

Lapa

2021

Cancers

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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.

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“…Various radiotracers for chemokine receptors, mostly labeled with radiometal, have previously been developed to visualize the inflammation mechanism involved in atherosclerosis [ 18 ]. [ 68 Ga]Ga-Pentixafor and [ 64 Cu]Cu-DOTA-DAPTA have successfully imaged inflammatory atherosclerosis via CXCR4 and CCR5 chemokine receptors, respectively [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and preclinical evaluation of a novel fluorine-18 labeled small-molecule PET radiotracer for imaging of CXCR3 receptor in mouse models of atherosclerosis

et al. 2023

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Background CXCR3 is a chemokine receptor and is expressed in innate and adaptive immune cells. It promotes the recruitment of T-lymphocytes and other immune cells to the inflammatory site in response to the binding of cognate chemokines. Upregulation of CXCR3 and its chemokines has been found during atherosclerotic lesion formation. Therefore, detection of CXCR3 by positron emission tomography (PET) radiotracer can be a useful tool for detecting the development of atherosclerosis in a noninvasive manner. Herein, we report the synthesis, radiosynthesis, and characterization of a novel fluorine-18 (F-18, 18F) labeled small-molecule radiotracer for the imaging of the CXCR3 receptor in mouse models of atherosclerosis. Results The reference standard 1 and its precursor 9 were synthesized over 5 steps from starting materials in good to moderate yields. The measured Ki values of CXCR3A and CXCR3B were 0.81 ± 0.02 nM and 0.31 ± 0.02 nM, respectively. [18F]1 was prepared by a two-step radiosynthesis with a decay-corrected radiochemical yield of 13 ± 2%, radiochemical purity > 99%, and specific activity of 44.4 ± 3.7 GBq/µmol at the end of synthesis (n = 6). The baseline studies showed that [18F]1 displayed high uptake in the atherosclerotic aorta and brown adipose tissue in Apolipoprotein E (ApoE) knockout (KO) mice fed with a high-fat diet over 12 weeks. The uptake of [18F]1 in these regions was reduced significantly in self-blocking studies, demonstrating CXCR3 binding specificity. Contrary to this, no significant differences in uptake of [18F]1 in the abdominal aorta of C57BL/6 control mice fed with a normal diet were observed in both baseline and blocking studies, indicating increased CXCR3 expression in atherosclerotic lesions. Immunohistochemistry studies demonstrated that [18F]1-positive regions were correlated with CXCR3 expression, but some atherosclerotic plaques with significant size were not detected by [18F]1, and their CXCR3 expressions were minimal. Conclusion [18F]1 was synthesized with good radiochemical yield and high radiochemical purity. In PET imaging studies, [18F]1 displayed CXCR3-specific uptake in the atherosclerotic aorta in ApoE KO mice. [18F]1 visualized CXCR3 expression in different regions in mice aligned with the tissue histology studies. Taken together, [18F]1 is a potential PET radiotracer for imaging CXCR3 in atherosclerosis.

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PET Imaging Radiotracers of Chemokine Receptors

Cited by 10 publications

References 158 publications

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

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

In Vivo Targeting of CXCR4—New Horizons

Synthesis and preclinical evaluation of a novel fluorine-18 labeled small-molecule PET radiotracer for imaging of CXCR3 receptor in mouse models of atherosclerosis

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