The aim of this study was to evaluate the novel probe 18 F-6-fluoro-N-[2-(diethylamino)ethyl] pyridine-3-carboxamide ( 18 F-MEL050) for the imaging of primary and metastatic melanoma. Methods: PET using 18 F-MEL050 was performed in murine models of melanoma. The specificity of 18 F-MEL050 was studied by comparing its accumulation in pigmented B16-F0 allograft tumors with that of human amelanotic A375 xenografts using PET and high-resolution autoradiography. 18 F-MEL050 PET results were compared with 18 F-FDG PET, the current standard in melanoma molecular imaging. To test the ability of 18 F-MEL050 to assess the metastatic spread of melanoma, a murine model of lung metastasis was imaged by PET/CT, and results correlated with physical assessment of tumor burden in the lungs. Results: In pigmented B16-F0 grafts, 18 F-MEL050 PET yielded a tumor-to-background ratio of approximately 20:1 at 1 h and greater than 50:1 at 2 and 3 h. In the B16-F0 melanoma allograft model, tumor-to-background ratio was more than 9-fold higher for 18 F-MEL050 than for 18 F-FDG (50.9 6 6.9 vs. 5.8 6 0.5). No uptake was observed in the amelanotic melanoma xenografts. Intense uptake of 18 F-MEL050 was evident in metastatic lesions in the lungs of B16-BL6 tumor-bearing mice on PET at 2 h after tracer injection, with high concordance between 18 F-MEL050 accumulation on PET/CT and tumor burden determined at necroscopy. Conclusion: 18 F-MEL050 has a rapid tumor uptake and high retention with specificity for melanin, suggesting great potential for noninvasive clinical evaluation of suspected metastatic melanoma.

The high melanoma uptake and rapid body clearance displayed by our series of [(123)I]iodonicotinamides prompted the development of [(18)F]N-(2-(diethylamino)ethyl)-6-fluoronicotinamide ([(18)F]2), a novel radiotracer for PET melanoma imaging. Significantly, unlike fluorobenzoates, [(18)F]fluorine incorporation on the nicotinamide ring is one step, facile, and high yielding. [(18)F]2 displayed high tumor uptake, rapid body clearance via predominantly renal excretion, and is currently being evaluated in preclinical studies for progression into clinical trials to assess the responsiveness of therapeutic agents.

of benzo[c]chromen-6-ones via novel cyclic aryl-Pd(II)-ester enolate Synthesis of benzo[c]chromen-6-ones via novel cyclic aryl-Pd(II)-ester enolate intermediates intermediates

The aim of this systematic review was to develop a thematic synthesis of existing qualitative studies to explore the use of humor in employee-to-employee workplace communication and provide a greater understanding of this area of research through the experiences of employees. A number of databases were searched using key terms and papers were selected using pre-specified criteria. The thematic synthesis approach of Thomas and Harden was used to review the final 23 papers. The findings from the thematic synthesis resulted in four temporal themes that described how humor was utilized during an employee’s organizational transition: (1) initiation into organizational humor, (2) joining a “tribe”—in-groups and out-groups, (3) exerting influence—humor as power, and (4) using the safety valve—humor to relieve tension. The temporal themes described in this study crossed organizational and cultural divides, where humor formed an essential part of work-based dialog.

18 F]6-Fluoro-N-[2-(diethylamino)ethyl]nicotinamide [ 18 F]MEL050 is a novel nicotinamide-based radiotracer, designed to target random metastatic dissemination of melanoma tumours by targeting melanin. Preclinical studies suggest that [ 18 F]MEL050 has an excellent potential to improve diagnosis and staging of melanoma. Here we report the radiochemical optimization conditions of [ 18 F]MEL050 and its large scale automated synthesis using a GE FX FN automated radiosynthesis module for clinical, phase-1 investigation. [ 18 F]MEL050 was prepared via a one-step synthesis using no-carrier added K[ 18 F]F-Krytpofix Ò 222 (DMSO, 1708C, 5 min) followed by HPLC purification. Using 6-chloro-N-[2-(diethylamino)ethyl]nicotinamide as precursor, [ 18 F]MEL050 was obtained in 40-46% radiochemical yield (non-decay corrected), in greater than 99.9% radiochemical purity and specific activity ranging from 240 to 325 GBq mmol À1 . Total synthesis time including formulation was 40 min and [ 18 F]MEL050 was stable (99.8%) in PBS for 6 h.