Abstract
The neuropeptide Y (NPY) Y-1, receptor (Y-1,R) selective radioligand (R)-N-a -(2,2-diphenylacety1)N-omega-[4(2[F-18]fluoropropanoylamino)butyllaminocarbonyl-N-(4-hydroxybenzy1)-argininamide ([F-18]23), derived from the high-affinity Y-1,R antagonist BIBP3226, was developed for imaging studies of Y-1,R-positive tumors. Starting from the argininamide core bearing amine-functionalized spacer ...
Abstract
The neuropeptide Y (NPY) Y-1, receptor (Y-1,R) selective radioligand (R)-N-a -(2,2-diphenylacety1)N-omega-[4(2[F-18]fluoropropanoylamino)butyllaminocarbonyl-N-(4-hydroxybenzy1)-argininamide ([F-18]23), derived from the high-affinity Y-1,R antagonist BIBP3226, was developed for imaging studies of Y-1,R-positive tumors. Starting from the argininamide core bearing amine-functionalized spacer moieties, a series of fluoropropanoylated and fluorobenzoylated derivatives was synthesized and studied for Y-1,R affinity. The fluoropropanoylated derivative 23 displayed high affinity (K-i = 1.3 nM) and selectivity toward Y1R Radiosynthesis was accomplished via F-18-fluoropropanoylation, yielding [F-18]23 with excellent stability in mice; however, the biodistribution study revealed pronounced hepatobiliary clearance with high accumulation in the gall bladder (>100 %ID/g). Despite the unfavorable biodistribution, [F-18]123 was successfully used for imaging of Y,R positive MCF-7 tumors in nude mice. Therefore, we suggest [F-18]23 as a lead for the design of PET ligands with optimized physicochemical properties resulting in more favorable biodistribution and higher Y-1,R-dependent enrichment in mammary carcinoma.
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