Folate Receptor β Targeted PET Imaging of Macrophages in Autoimmune Myocarditis

Rationale: Currently available imaging techniques have limited specificity for the detection of active myocardial inflammation. Aluminum fluoride-18-labeled 1,4,7-triazacyclononane-N,N′,N″-triacetic acid conjugated folate (18F-FOL) is a positron emission tomography (PET) tracer targeting folate receptor β (FR-β) that is expressed on activated macrophages at sites of inflammation. We evaluated 18F-FOL PET for the detection of myocardial inflammation in rats with autoimmune myocarditis and studied expression of FR-β in human cardiac sarcoidosis specimens. Methods: Myocarditis was induced by immunizing rats (n = 18) with porcine cardiac myosin in complete Freund’s adjuvant. Control rats (n = 6) were injected with Freund’s adjuvant alone. 18F-FOL was intravenously injected followed by imaging with a small animal PET/computed tomography (CT) scanner and autoradiography. Contrast-enhanced high-resolution CT or 2-deoxy-2-18F-fluoro-D-glucose (18F-FDG) PET images were used for co-registration. Rat tissue sections and myocardial autopsy samples of 6 patients with cardiac sarcoidosis were studied for macrophages and FR-β. Results: The myocardium of 10 out of 18 immunized rats showed focal macrophage-rich inflammatory lesions with FR-β expression occurring mainly in M1-polarized macrophages. PET images showed focal myocardial 18F-FOL uptake co-localizing with inflammatory lesions (SUVmean, 2.1 ± 1.1), whereas uptake in the remote myocardium of immunized rats and controls was low (SUVmean, 0.4 ± 0.2 and 0.4 ± 0.1, respectively; P </p

Aluminum fluoride-18 labeled folate enables in vivo detection of atherosclerotic plaque inflammation by positron emission tomography

Inflammation plays an important role in the development of atherosclerosis and its complications. Because the folate receptor beta (FR-beta) is selectively expressed on macrophages, an FR targeted imaging agent could be useful for assessment of atherosclerotic inflammation. We investigated aluminum fluoride-18-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid conjugated folate (F-18-FOL) for the detection of atherosclerotic plaque inflammation. We studied atherosclerotic plaques in mice, rabbits, and human tissue samples using F-18-FOL positron emission tomography/computed tomography (PET/CT). Compound 2-deoxy-2-[F-18]fluoro-D-glucose (F-1(8)-FDG) was used as a comparison. Firstly, we found that the in vitro binding of F-18-FOL co-localized with FR-beta-positive macrophages in carotid endarterectomy samples from patients with recent ischemic symptoms. We then demonstrated specific accumulation of intravenously administered F-18-FOL in atherosclerotic plaques in mice and rabbits using PET/CT. We noticed that the F-18-FOL uptake correlated with the density of macrophages in plaques and provided a target-to-background ratio as high as F-18-FDG, but with considerably lower myocardial uptake. Thus, F-18-FOL PET/CT targeting of FR-beta-positive macrophages presents a promising new tool for the in vivo imaging of atherosclerotic inflammation

Screening strategies for thyroid disorders in the first and second trimester of pregnancy in China.

Thyroid dysfunction during pregnancy is associated with multiple adverse outcomes, but whether all women should be screened for thyroid disorders during pregnancy remains controversial.To evaluate the effectiveness of the targeted high risk case-finding approach for identifying women with thyroid dysfunction during the first and second trimesters of pregnancy.Levels of thyroid stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibodies (TPOAb) were measured in 3882 Chinese women during the first and second trimester of pregnancy. All tested women were divided into the high risk or non-high risk groups, based on their history, findings from physical examination, or other clinical features suggestive of a thyroid disorder. Diagnosis of thyroid disorders was made according to the standard trimester-specific reference intervals. The prevalence of thyroid disorders in each group was determined, and the feasibility of a screening approach focusing exclusively on high risk women was evaluated to estimate the ability of finding women with thyroid dysfunction.The prevalence of overt hypothyroidism or hyperthyroidism in the high risk group was higher than in the non-high risk group during the first trimester (0.8% vs 0, χ2 = 7.10, p = 0.008; 1.6% vs 0.2%, χ2 = 7.02, p = 0.008, respectively). The prevalence of hypothyroxinemia or TPOAb positivity was significantly higher in the high risk group than in the non-high risk group during the second trimester (1.3% vs 0.5%, χ2 = 4.49, p = 0.034; 11.6% vs 8.4%, χ2 = 6.396, p = 0.011, respectively). The total prevalence of hypothyroidism or hyperthyroidism and the prevalence of subclinical hypothyroidism or hyperthyroidism were not statistically different between the high risk and non-high risk groups, for either the first or second trimester.The high risk screening strategy failed to detect the majority of pregnant women with thyroid disorders. Therefore, we recommend universal screening of sTSH, FT4, and TPOAb during the first trimester and second trimester of pregnancy

Risk factors of thyroid disorders in the second trimester (n %).

<p>Risk factors of thyroid disorders in the second trimester (n %).</p

Prevalence of thyroid disorders in the second trimester (n, %).

<p>Prevalence of thyroid disorders in the second trimester (n, %).</p

Demographic characteristics of the pregnant women in this study (n = 3882).

<p>Notes: Data are presented as mean±SD, first trimester vs. second trimester ^**<i>p</i><0.000, ^*<i>p</i><0.01, ^△<i>p</i><0.05.</p

Risk factors of thyroid disorders in the first trimester (n, %).

<p>Risk factors of thyroid disorders in the first trimester (n, %).</p

Prevalence of thyroid disorders in the first trimester (n, %).

<p>Prevalence of thyroid disorders in the first trimester (n, %).</p