Molecular Imaging of the Chemokine Receptor CXCR4 After Acute Myocardial Infarction

Abstract

Targeted PET imaging with (68)Ga-pentixafor identifies the global and regional CXCR4 expression pattern in myocardium and systemic organs. CXCR4 upregulation after AMI coincides with inflammatory cell infiltration, but shows interindividual variability in patients. This may have implications for the response to CXCR4- or other inflammation-targeted therapy, and for subsequent ventricular remodeling.

Imaging of Post-Infarct Inflammation

“…Further steps may include the evaluation of tracers other than FDG, such as the amino acid methionine 16 or the chemokine-targeted agent pentixafor. 17 In parallel, early inflammation-targeted molecular imaging may be implemented in larger post-AMI outcome registries to bolster the notion of its predictive value. Finally, this new imaging approach seems to be ready for implementation as a surrogate end point in clinical trials of novel therapies targeting post-infarct inflammation and myocardial repair.…”

The Role of Attractiveness: Imaging the Interaction Between Cardiovascular and Immune System

“…It may, however, also be a disadvantage because minor changes of one chemokine receptor may be masked or even counterregulated by changes in other receptors, making the detection of subtle differences difficult. Other groups and prior work of the same group, for example, chose to focus on specific chemokine receptors such as CXCR4 or CCR5 and explored their role in cardiovascular disease (16,17). Another aspect that is promising and challenging at the same time is the use of nanoparticles and 64 Cu for labeling.…”

Specificity vs versatility: A fine balance for novel targeted molecular imaging radiotracers

“…In recent years, a widening array of novel or repurposed tracers targeted to specific physiologic mechanisms, cell types, or receptors have emerged to evaluate various components of the disease process. To this end, recent studies have evaluated novel tracers targeting chemokine receptors on leukocytes (e.g., 68 Ga-pentixafor), 2 somatostatin receptors on activated macrophages (e.g., 68 Ga-DOTATATE), 3 mannose receptor on M2-polarized macrophages (e.g.,…”

“…Outcome-based strategies are paramount-the ability to detect a difference in tracer binding between health and disease states is only the first step; rather, it is essential that a candidate tracer determines not only the presence of abnormalities, but also defines the prognostic value or evaluate the resolution of these abnormalities by therapeutic intervention. 2,7,15 It appears that 11 C-TZ3321 can distinguish between mild (wild-type) and more severe (ApoE -/-) neointimal hyperplasia (albeit with limited binding in the mild phenotype), but it will be important to determine whether the tracer has sufficient sensitivity to identify mild vascular smooth muscle proliferation before overt disease. The molecular targeting of the tracer underlies the potential to exceed identification of restenosis by anatomical imaging alone.…”

“…For example, the CXCR4-specific 68 Ga-pentixafor in vivo PET signal was responsive to anti-inflammatory therapy in mice after myocardial infarction, 2 and 18 F-galacto-RGD uptake in atherosclerotic plaques declined after cessation of atherogenic diet in mice. 16 Pharmacological blockade of S1P 1 by FTY720 after femoral artery denudation is a logical next step, and may provide valuable insight into the sensitivity of the tracer and its suitability for monitoring therapeutic efficacy.…”