Discovery of [18F]N-(2-(Diethylamino)ethyl)-6-fluoronicotinamide: A Melanoma Positron Emission Tomography Imaging Radiotracer with High Tumor to Body Contrast Ratio and Rapid Renal Clearance

• Published in: Journal of medicinal chemistry Vol. 52; no. 17; pp. 5299 - 5302
• Main Authors: Greguric, Ivan, Taylor, Stephen R, Denoyer, Delphine, Ballantyne, Patrice, Berghofer, Paula, Roselt, Peter, Pham, Tien Q, Mattner, Filomena, Bourdier, Thomas, Neels, Oliver C, Dorow, Donna S, Loc’h, Christian, Hicks, Rodney J, Katsifis, Andrew
• Format: Journal Article
• Language: English
• Published: Columbus, OH American Chemical Society 10-09-2009
• Subjects: Animals; Biological and medical sciences; Contrast media. Radiopharmaceuticals; Drug Discovery; Humans; Kidney - metabolism; Medical sciences; Melanoma - diagnostic imaging; Melanoma - metabolism; Metabolic Clearance Rate; Mice; Niacinamide - analogs & derivatives; Niacinamide - analysis; Niacinamide - chemical synthesis; Niacinamide - pharmacokinetics; Pharmacology. Drug treatments; Positron-Emission Tomography; Radioactive Tracers; Radiochemistry; Tissue Distribution; Intravenous administration; Fluorine 18; Spontaneous; Clearance; Pyridine derivatives; Tissue; Scintigraphic agent; Imaging; B16-Melanoma; Malignant melanoma; Chemical synthesis; Human; Fluorine Isotopes; Radiolabelling; Rodentia; Elimination; Malignant tumor; Uptake; Vertebrata; Mammalia; Mouse; Animal; Distribution; Tertiary amine; Carboxamide; Pharmacokinetics; Positron emission tomography; Cancer
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm9008423

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.