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A series of 2,6-disubstituted indenofluorene derivatives were obtained in high purity via a general route involving the Suzuki coupling reaction. The potential of these conjugated indenofluorenes as new organic semiconductors was demonstrated by the light-emitting diode reaching a high luminance of 1400 Cd/m 2 below 10 V.Conjugated aromatic compounds are potential candidates as organic semiconductors for use in thin-film transistors (TFTs) and light-emitting diodes (LEDs). By incorporation of strongly electronegative substituents such as fluorine 1 and cyano groups 2 into certain aromatic molecules, some important n-type compounds have been obtained for TFT applications. To develop organic LED devices (OLEDs) with uniform luminescence, saturated color, and low driving voltages, many material factors must be considered, such as emission efficiency, color purity, carrier mobility, thermal and chemical stability, and processability (for vapor-phase deposition). 3 Among those organic semiconductors known for transistor and OLED applications, the fluorene-based compounds, 4 oligomers, 5 and polymers 6 have received most attention, owing to their unique properties, availability, and processability. Since the substituted fluorenes are known to have relatively high band gaps and low HOMO levels, they are

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Cell therapy is expected to restore perfusion and improve function in the ischemic/infarcted myocardium; however, the biological mechanisms and local effects of transplanted cells remain unclear. To assess cell fate in vivo, hexadecyl-4-[18F]fluorobenzoate (18F-HFB) cell labeling was evaluated for tracking human circulating progenitor cells (CPCs) with positron emission tomography (PET) and was compared to the commonly used 2-[18F]fluoro-2-deoxy-d-glucose (18F-FDG) labeling method in a rat myocardial infarction model. CPCs were labeled with 18F-HFB or 18F-FDG ex vivo under the same conditions. 18F-HFB cell-labeling efficiency (23.4 ± 7.5%) and stability (4 h, 88.4 ± 6.0%) were superior to 18F-FDG (7.6 ± 4.1% and 26.6 ± 6.1%, respectively; p < 0.05). Neither labeling approach significantly altered cell viability, phenotype or migration potential up to 24 h postlabeling. Two weeks after left anterior descending coronary artery ligation, rats received echo-guided intramyocardial injection in the infarct border zone with 18F-HFB-CPCs, 18F-FDG-CPCs, 18F-HFB, or 18F-FDG. Dynamic PET imaging of both 18F-HFB-CPCs and 18F-FDG-CPCs demonstrated that only 16–37% of the initial injection dose (ID) was retained in the injection site at 10 min postdelivery, and remaining activity fell significantly over the first 4 h posttransplantation. The 18F-HFB-CPC signal in the target area at 2 h (23.7 ± 14.7% ID/g) and 4 h (17.6 ± 13.3% ID/g) postinjection was greater than that of 18F-FDG-CPCs (5.4 ± 2.3% ID/g and 2.6 ± 0.7% ID/g, respectively; p < 0.05). Tissue biodistribution confirmed the higher radioactivity in the border zone of 18F-HFB-CPC rats. Immunostaining of heart tissue sections revealed no significant difference in cell retention between two labeled cell transplantation groups. Good correlation with biodistribution results was observed in the 18F-HFB-CPC rats (r = 0.81, p < 0.05). Compared to 18F-FDG, labeling human CPCs with 18F-HFB provides a more efficient, stable, and accurate way to quantify the distribution of transplanted cells. 18F-HFB cell labeling with PET imaging offers a better modality to enhance our understanding of early retention, homing, and engraftment with cardiac cell therapy.

Most physiologic effects of the renin angiotensin system (RAS) are mediated via the angiotensin (Ang) type 1 receptor (AT 1 R). The 18 FFPyKYNE derivative of the clinically used AT 1 R blocker losartan exhibits high binding selectivity for kidney AT 1 R and rapid metabolism in rats. The aim of this study was to further assess the binding profile of this novel PET agent for imaging AT 1 R in rats and pigs. Methods: In vitro binding assays were performed with 18 F-FPyKYNElosartan in rat kidneys. Male Sprague-Dawley rats were used to assess dosimetry, antagonistic efficacy via blood pressure measurements, and presence of labeled metabolites in kidneys. Testretest PET imaging, blocking with AT 1 R antagonist candesartan (10 mg/kg), and plasma metabolism analysis were performed in female Yorkshire pigs. Results: 18 F-FPyKYNE-losartan bound with high affinity (dissociation constant of 49.4 ± 18.0 nM and maximal binding of 348 ± 112 fmol/mm 2 ) to rat kidney AT 1 R. It bound strongly to plasma proteins in rats (97%), and its labeled metabolites displayed minimal interference on renal AT 1 R binding. FPyKYNE-losartan fully antagonized the Ang II pressor effect, albeit with 4-fold potency reduction (the effective dose inhibiting 50% of the Ang II-induced maximal pressor response of 25.5 mg/kg) relative to losartan. PET imaging exhibited high kidney-to-blood contrast and slow renal clearance, with an SUV of 14.1 ± 6.2. Excellent reproducibility was observed in the calculated test-retest variability (7.2% ± 0.75%). Only hydrophilic-labeled metabolites were present in plasma samples, and renal retention was reduced (−60%) at 10-15 min after blockade with candesartan. Conclusion: 18 F-FPyKYNE-losartan has a favorable binding profile and displays high potential for translational work in humans as an AT 1 R PET imaging agent.

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The renin-angiotensin system regulates blood pressure via activation of the angiotensin II type 1 receptor (AT 1 R). The AT 1 R is involved in the pathology of cardiac and renal diseases such as heart failure and diabetic nephropathy. The aim of this study was to synthesize and characterize the O-[ 11 C]methylated derivative of the clinically used AT 1 receptor blocker losartan as a novel AT 1 R PET imaging radioligand. [ 11 C]Methyl-losartan was reliably synthesized (n≥40) via methylation of tetrazoleprotected losartan followed by deprotection using HCl in an overall yield of 30%-60% (decay-corrected from [11 C]MeI). Radiochemical purity was >99% and specific activity 700-3600mCi/mmol.