Radiosynthesis and biological evaluation of [68Ga]Ga-NOTA-Folate in experimental atherosclerosis and myocardial infarction models.

While many folate-receptor (FR) targeting radiotracers have been studied for imaging cancers, there is a need for tracers that target inflammation for diagnostic and monitoring purposes. Two diseases in which inflammation plays a key role are atherosclerosis and myocardial infarction (MI). Inflammation is critical to the development and progression of atherosclerosis, which can lead to MI. Higher macrophage levels have been associated with adverse remodeling effects in post-MI healing. Given the commonality of these potentially fatal conditions, it is of great interest to have a reliable radiotracer available for non-invasive detection and monitoring. As FR-β expression is upregulated in active macrophages, it serves as a great target for imaging of inflammation. [68Ga]Ga-NOTA-Folate, a new FR-targeting radiotracer, was synthesized and biologically evaluated to assess its ability to target inflammation in mouse and human atherosclerotic lesions. Mice were studied using in vivo positron emission tomography and ex vivo digital autoradiography of aorta sections. Human carotid artery tissues were studied in vitro for tracer binding. In addition, rat heart tissue sections were incubated in vitro with [68Ga]Ga-NOTA-Folate to evaluate post-MI healing. Upon analyzing the in vitro binding, [68Ga]Ga-NOTA-Folate showed significantly higher binding in atherosclerotic lesions when compared to tissues treated with folate glucosamine, a FR blocker, indicating specificity of [68Ga]Ga-NOTA-Folate via FRs. As the atherosclerotic lesions observed in the experimental mice were not so extensive, more in vivo studies should be done to verify the results

[C-11]carfentanil PET imaging for studying the peripheral opioid system in vivo : effect of photoperiod on mu-opioid receptor availability in brown adipose tissue

Purpose Photoperiod determines the metabolic activity of brown adipose tissue (BAT) and affects the food intake and body mass of mammals. Sympathetic innervation of the BAT controls thermogenesis and facilitates physiological adaption to seasonal changes, but the exact mechanism remains elusive. Previous studies have shown that central opioid signaling regulates BAT thermogenesis, and that the expression of the brain mu-opioid receptor (MOR) varies seasonally. Therefore, it is important to know whether MOR expression in BAT shows seasonal variation. Methods We determined the effect of photoperiod on BAT MOR availability using [C-11] carfentanil positron emission tomography (PET). Adult rats (n = 9) were repeatedly imaged under various photoperiods in order to simulate seasonal changes. Results Long photoperiod was associated with low MOR expression in BAT (beta = -0.04, 95% confidence interval: - 0.07, - 0.01), but not in muscles. We confirmed the expression of MOR in BAT and muscle using immunofluorescence staining. Conclusion Photoperiod affects MOR availability in BAT. Sympathetic innervation of BAT may influence thermogenesis via the peripheral MOR system. The present study supports the utility of [C-11]carfentanil PET to study the peripheral MOR system.Peer reviewe

[11C]carfentanil PET imaging for studying the peripheral opioid system in vivo: effect of photoperiod on mu-opioid receptor availability in brown adipose tissue

Purpose Photoperiod determines the metabolic activity of brown adipose tissue (BAT) and affects the food intake and body mass of mammals. Sympathetic innervation of the BAT controls thermogenesis and facilitates physiological adaption to seasonal changes, but the exact mechanism remains elusive. Previous studies have shown that central opioid signaling regulates BAT thermogenesis, and that the expression of the brain mu-opioid receptor (MOR) varies seasonally. Therefore, it is important to know whether MOR expression in BAT shows seasonal variation.Methods We determined the effect of photoperiod on BAT MOR availability using [C-11] carfentanil positron emission tomography (PET). Adult rats (n = 9) were repeatedly imaged under various photoperiods in order to simulate seasonal changes.Results Long photoperiod was associated with low MOR expression in BAT (beta = -0.04, 95% confidence interval: - 0.07, - 0.01), but not in muscles. We confirmed the expression of MOR in BAT and muscle using immunofluorescence staining.Conclusion Photoperiod affects MOR availability in BAT. Sympathetic innervation of BAT may influence thermogenesis via the peripheral MOR system. The present study supports the utility of [C-11]carfentanil PET to study the peripheral MOR system.</p