Cardiac DPD-uptake time dependency in ATTR patients verified by quantitative SPECT/CT and semiquantitative planar parameters.

BACKGROUND: Bone scintigraphy plays an important role in the diagnosis of cardiac Transthyretin-Related Amyloidosis (ATTR). The mechanism of myocardial tracer accumulation and its dependence over time are not fully understood. Recently, a scintigraphic quantification of the cardiac amyloid deposition has been discussed. Nevertheless, little is known regarding the right time of quantitative imaging. METHODS: The geometrical mean of decay corrected total counts over the heart and the heart/whole-body ratio (H/WB) were evaluated in 23 patients undergoing DPD-bone scan with planar whole-body images 1 and 3 hours post injection (p.i.). Myocardial standard uptake values (SUV)peak were assessed in another 15 patients with quantitative SPECT/CT imaging 1 hours and 3 hours p.i.. RESULTS: Total counts over the heart (1 hours p.i.: 81,676 cts, range 69,887 to 93,091 cts and 3 hours p.i.: 64,819 cts, range 52,048 to 86,123 cts, P = .0005) and H/WB ratio (1 hours p.i.:0.076 ± 0.020 and 3 hours p.i. 0.070 ± 0.022; P = .0003) were significantly increased 1 hours p.i.. Furthermore median myocardial SUVpeak (1 hours p.i.:12.2, range 9.6 to 18.9 and 3 hours p.i.: 9.6, range 8.2 to 15.0, P = 0.0012) was also significantly higher after 1 hours p.i. compared to 3 hours p.i.. CONCLUSION: Cardiac DPD activity and myocardial SUVpeak are time-dependent, which should be considered when using quantitative bone scintigraphy in ATTR patients.

Intact vitamin A transport is critical for cold-mediated adipose tissue browning and thermogenesis.

OBJECTIVE: Transformation of white into brown fat ("browning") reduces obesity in many preclinical models and holds great promise as a therapeutic concept in metabolic disease. Vitamin A metabolites (retinoids) have been linked to thermogenic programming of adipose tissue; however, the physiologic importance of systemic retinoid transport for adipose tissue browning and adaptive thermogenesis is unknown. METHODS: We performed cold exposure studies in mice and humans and used a genetic model of defective vitamin A transport, the retinol binding protein deficient (Rbp-/-) mouse, to study the effects of cooling on systemic vitamin A and the relevance of intact retinoid transport on cold-induced adipose tissue browning. RESULTS: We show that cold stimulation in mice and humans leads to an increase in circulating retinol and its plasma transporter, Rbp. In Rbp-/- mice, thermogenic programming of adipocytes and oxidative mitochondrial function are dramatically impaired in subcutaneous white fat, which renders Rbp-/- mice more cold-sensitive. In contrast, retinol stimulation in primary human adipocytes promotes thermogenic gene expression and mitochondrial respiration. In humans, cold-mediated retinol increase is associated with a shift in oxidative substrate metabolism suggestive of higher lipid utilisation. CONCLUSIONS: Systemic vitamin A levels are regulated by cold exposure in mice and humans, and intact retinoid transport is essential for cold-induced adipose tissue browning and adaptive thermogenesis.

In vitro Radiopharmaceutical Evidence for MCHR1 Binding Sites in Murine Brown Adipocytes.

[11C]SNAP-7941 and its radiofluorinated, fluoro-ethyl derivative [18F]FE@SNAP have been developed as the first positron emission tomography tracers for melanin-concentrating hormone receptor 1 (MCHR1) imaging. Accumulation of these MCHR1 PET-tracers in rat brown adipose tissue (BAT) in vivo provided first indication of MCHR1 expression in rodent BAT. To rule out off-target binding, affinity of both MCHR1 ligands toward adrenergic beta-3 receptors (ADRB3) was examined. Further, specific binding of [11C]SNAP-7941 to brown adipocytes and effects of MCHR1 ligands on brown adipocyte activation were investigated. SNAP-7941 and FE@SNAP evinced to be highly selective toward MCHR1. [11C]SNAP-7941 binding to brown adipocytes was shown to be mainly MCHR1-specific. This data strongly indicates MCHR1 expression in rodent BAT and moreover, a peripheral, anti-obesity effect of MCHR1 antagonists directly exerted in BAT is proposed. Moreover, MCHR1 expression in murine brown adipocytes was confirmed by protein and mRNA analysis. We conclude that MCHR1 PET imaging contributes to basic research in endocrinology by elucidating the involvement of the MCH system in peripheral tissues, such as BAT.