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

Abstract

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.

Improved Detection of Regional Melanoma Metastasis Using 18F-6-Fluoro-N-[2-(Diethylamino)Ethyl] Pyridine-3-Carboxamide, a Melanin-Specific PET Probe, by Perilesional Administration

“…18 F-MEL050 was labeled in an in-house radiochemistry facility, as previously described (15). Briefly, 18 F-MEL050 was prepared from 6-chloro-N-[2-(diethylamino)ethyl] pyridine-3-carboxamide precursor by a 1-step radiosynthesis using no-carrier-added 18 F-KF-Krytpofix 222 (dimethylformamide, 150°C, 5 min), followed by high-performance liquid chromatography purification.…”

“…Recently, we reported the synthesis of 18 F-6-fluoro-N-[2-(diethylamino)ethyl] pyridine-3-carboxamide ( 18 F-MEL050), a new melanoma PET probe with high specificity and avidity for melanin (15). We assessed the imaging potential of 18 F-MEL050 using small-animal PET in the B16 model of murine malignant melanoma (16).…”

Melanoma Imaging with Highly Specific PET Probes: Ready for Prime Time?

“…As a consequence of the limited benefit of 18 F-FDG in evaluating sentinel nodes, the desire to successfully combat recurrent and metastatic melanoma has sparked interest in the development of tracers relating to specific characteristics of melanoma cells (10)(11)(12). A class of compounds that depicts melanin biosynthesis and metallopeptide binding to melanocortin type 1 receptors overexpressed in melanomas belongs to this category of novel and promising agents, and antibody and angiogenesis imaging continue to reside in the arena of research and development.…”

4-11C-Methoxy N-(2-Diethylaminoethyl) Benzamide: A Novel Probe to Selectively Target Melanoma

“…Nonetheless, its synthesis takes approximately 3 h and 2 or more purifications (10,11). Recently, several other 18 F-benzamides were evaluated to assess their potential to target melanoma (12)(13)(14)(15). Although the synthesis time of MEL050 (12) and 18 F-FPDA (15) was shorter, the in vitro and in vivo properties of these benzamides were even less optimal than that of 18 F-DAFBA.…”

“…Recently, several other 18 F-benzamides were evaluated to assess their potential to target melanoma (12)(13)(14)(15). Although the synthesis time of MEL050 (12) and 18 F-FPDA (15) was shorter, the in vitro and in vivo properties of these benzamides were even less optimal than that of 18 F-DAFBA. Therefore, to develop a probe with facile radiochemical synthesis while bearing biologic properties similar to or better than 18 F-DAFBA, we focused our efforts toward developing its 11 C analog.…”