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Article Abstract
Cardiac amyloidosis (CA) is a complex restrictive cardiomyopathy, and while treatment options are advancing rapidly, specific diagnostic probes for CA have rarely been developed or reported. In this study, a series of pyridinium styryl derivatives were designed and synthesized, exhibiting specific affinity for immunoglobulin light chain protein amyloidosis (AL). Through a structure-activity relationship analysis and bioevaluations, [F] was identified as the first candidate for PET/CT imaging in rodents. However, due to its increasing lipophilicity, the uptake in healthy myocardium remained high (SUV = 3.8) during imaging, making it unsuitable for detecting myocardial amyloidosis. Subsequently, we rationally designed and optimized the second candidate, [Ga], maintaining moderate affinity (IC = 134.3 nM) while increasing hydrophilicity. Compound [Ga] successfully labeled AL deposits on myocardial slices and demonstrated rapid clearance from healthy myocardium. Overall, [Ga] represents a promising PET tracer for CA imaging and warrants further clinical evaluation.
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| http://dx.doi.org/10.1021/acs.jmedchem.5c01485 | DOI Listing |
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