Nuclear (PET/SPECT) and optical imaging probes targeting the CXCR4 chemokine receptor

Abstract

The chemokine receptor CXCR4 has been found to be highly expressed in a wide variety of cancer types, including breast, colorectal, melanoma, nasopharyngeal, oesophageal, osteosarcoma, and nonsmall-cell lung carcinoma. It has been shown that these elevated expression levels are yet further increased upon metastasis. This receptor therefore represents a highly attractive target which could facilitate the diagnostic imaging of many aggressive cancers. Since 2005, there have been a wide assortment of CXCR4-targeting imaging probes spanning both nuclear (PET/SPECT) and optical imaging modalities. This review highlights a wide variety of pertinent examples from the recent literature, placing special focus on the chemical aspects of probe design. James C: Knight Dr James C. Knight obtained a BSc in chemistry from Cardiff University in 2005 and subsequently a PhD in 2009 under the supervision of Dr Angelo J. Amoroso and Prof. Peter G. Edwards. He subsequently spent two years working between the Cardiff School of Biosciences and Chemistry departments developing multimodal imaging agents under the supervision of

Synthesis, characterisation and evaluation of a novel copper-64 complex with selective uptake in EMT-6 cells under hypoxic conditions

“…The success of PET imaging is dependent upon the use of specifically designed molecular probes which have the ability to accumulate at particular targets associated with disease (e.g. up-regulated glucose metabolism, 2 hypoxic microenvironment within tumors, 3 and certain cellular or chemical biomarkers 4 ). Consequently, the development of molecular probes containing positron emitting radionuclides is an area of intense multidisciplinary research.…”

68Ga-Pentixafor PET/CT Demonstrating In Vivo CXCR4 Receptor Overexpression in Rare Lung Malignancies: Correlation with Histologic and Histochemical Findings

“…However, the pattern of uptake and the in vivo evidence of CXCR4 expression in rare lung malignancies have not been studied before. 68 Ga-pentixafor PET tracer was shown to have excellent affinity for CXCR4 receptors in preclinical and clinical studies (19,20). According to the available literature, noninvasive imaging of CXCR4 expression in SCLC is feasible, and 68 Ga-pentixafor as a novel PET tracer might serve as a readout for confirming the CXCR4 expression (20).…”

Positron Emission Tomographic Imaging of CXCR4 in Cancer: Challenges and Promises

“…Among the various strategies developed to image CXCR4 noninvasively, this review article focuses on the development of positron emission tomography (PET) radiotracers. 70,[73][74][75] PET can significantly contribute to the clinical management of a patient by providing early functional data on disease extent, therapy response, and identification of recurrence and can also be used for therapy planning. Technological advances in PET instrumentation have enabled the transition of human imaging capabilities to the scale of small animals, [76][77][78] and PET imaging is now recognized as a major translational ''bench to bedside'' molecular imaging approach due to its high sensitivity, together with the large variety and increasing portfolio of tracers for the monitoring of key biological processes in cancer.…”