Browsing by Author "Taylor, SR"

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    Discovery of [F-18]N-(2-(Diethylamino)ethyl)-6-fluoronicotinamide: a melanoma positron emission tomography imaging radiotracer with high tumor to body contrast ratio and rapid renal clearance
    (American Chemical Society, 2009-09-10) Greguric, I; Taylor, SR; Denoyer, D; Ballantyne, P; Berghofer, PJ; Roselt, P; Pham, TQ; Mattner, F; Bourdier, T; Neels, OC; Dorow, DS; Loc'h, C; Hicks, RJ; Katsifis, A
    The high melanoma uptake and rapid body clearance displayed by our series of [123I]iodonicotinamides prompted the development of [18F]N-(2-(diethylamino)ethyl)-6-fluoronicotinamide ([18F]2), a novel radiotracer for PET melanoma imaging. Significantly, unlike fluorobenzoates, [18F]fluorine incorporation on the nicotinamide ring is one step, facile, and high yielding. [18F]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. © 2009, American Chemical Society
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    High-contrast PET of melanoma using F-18-MEL050, a selective probe for melanin with predominantly renal clearance
    (Society of Nuclear Medicine, 2010-03) Denoyer, D; Greguric, I; Roselt, P; Neels, OC; Aide, N; Taylor, SR; Katsifis, A; Dorow, DS; Hicks, RJ
    The aim of this study was to evaluate the novel probe 18F-6-fluoro-N-[2-(diethylamino)ethyl] pyridine-3-carboxamide (18F-MEL050) for the imaging of primary and metastatic melanoma. Methods: PET using 18F-MEL050 was performed in murine models of melanoma. The specificity of 18F-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. 18F-MEL050 PET results were compared with 18F-FDG PET, the current standard in melanoma molecular imaging. To test the ability of 18F-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, 18F-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 18F-MEL050 than for 18F-FDG (50.9 ± 6.9 vs. 5.8 ± 0.5). No uptake was observed in the amelanotic melanoma xenografts. Intense uptake of 18F-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 18F-MEL050 accumulation on PET/CT and tumor burden determined at necroscopy. Conclusion: 18F-MEL050 has a rapid tumor uptake and high retention with specificity for melanin, suggesting great potential for noninvasive clinical evaluation of suspected metastatic melanoma. © 2010, Society of Nuclear Medicine
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    Synthesis and in vivo evaluation of [123I]melanin-targeted agents
    (American Chemical Society, 2015-08-15) Roberts, MP; Nguyen, VH; Ashford, ME; Berghofer, PJ; Wyatt, NA; Krause-Heuer, AM; Pham, TQ; Taylor, SR; Hogan, L; Jiang, CD; Fraser, BH; Lengkeek, NA; Matesic, L; Grégoire, MC; Denoyer, D; Hicks, RJ; Katsifis, A; Greguric, I
    This study reports the synthesis, [123I]radiolabeling, and biological profile of a new series of iodinated compounds for potential translation to the corresponding [131I]radiolabeled compounds for radionuclide therapy of melanoma. Radiolabeling was achieved via standard electrophilic iododestannylation in 60–90% radiochemical yield. Preliminary SPECT imaging demonstrated high and distinct tumor uptake of all compounds, as well as high tumor-to-background ratios compared to the literature compound [123I]4 (ICF01012). The most favorable compounds ([123I]20, [123I]23, [123I]41, and [123I]53) were selected for further biological investigation. Biodistribution studies indicated that all four compounds bound to melanin containing tissue with low in vivo deiodination; [123I]20 and [123I]53 in particular displayed high and prolonged tumor uptake (13% ID/g at 48 h). [123I]53 had the most favorable overall profile of the cumulative uptake over time of radiosensitive organs. Metabolite analysis of the four radiotracers found [123I]41 and [123I]53 to be the most favorable, displaying high and prolonged amounts of intact tracer in melanin containing tissues, suggesting melanin specific binding. Results herein suggest that compound [123I]53 displays favorable in vivo pharmacokinetics and stability and hence is an ideal candidate to proceed with further preclinical [131I] therapeutic evaluation. ©2015, American Chemical Society
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    Synthesis and radiosynthesis of a novel PET fluorobenzyl piperazine for melanoma tumour imaging; [18F]MEL054
    (CSIRO publishing, 2012-02-18) Taylor, SR; Roberts, MR; Wyatt, NA; Pham, TQ; Stark, D; Bourdier, T; Roselt, P; Katsifis, A; Greguric, I
    2-{2-[4-(4-[18F]-Fluorobenzyl)piperazin-1-yl]-2-oxoethyl}isoindolin-1-one ([18F]MEL054), is a new potent indolinone-based melanin binder designed to target melanotic tumours. [18F]MEL054 was prepared by an automated two-step radiosynthesis, comprising of the preparation of 4-[18F]fluorobenzaldehyde from 4-formyl-N,N,N-trimethylanilinium triflate, followed by reductive alkylation with 2-(2-oxo-2-piperazin-1-ylethyl)isoindolin-1-one. 4-[18F]Fluorobenzaldehyde was prepared on a GE TRACERlab FXFN module in 68 ± 8 % radiochemical yield (RCY, non-decay corrected), purified by a Sep-Pak Plus C18 cartridge and eluted into the reactor of an in-house modified Nuclear Interface [18F]FDG synthesis module for the subsequent reductive alkylation reaction. HPLC purification produced [18F]MEL054 in a collected RCY of 34 ± 9 % (non-decay corrected), the total preparation time (including Sep-Pak Plus C18 and HPLC purification) did not exceed 105 min. The radiochemical purity of [18F]MEL054 was greater than 99 % with a specific radioactivity of 71–119 GBq μmol–1 and [18F]MEL054 remained stable in saline solution (>98 %) after 3 h. © 2013 CSIRO.