Purpose <p>This study aimed to evaluate the feasibility and diagnostic utility of a dual-target positron emission tomography (PET) imaging approach using a cocktail of N-3-[¹⁸F]fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ([¹⁸F]FP-CIT) and [¹⁸F]florbetaben (FBB) for the simultaneous assessment of dopaminergic and amyloid changes in a preclinical setting.</p> Procedures <p>We utilized both Parkinson’s disease (PD) and Alzheimer’s disease (AD) mouse models, as well as a control group, to investigate the uptake of [¹⁸F]FP-CIT and [¹⁸F]FBB individually and in combination. PET imaging was conducted, and standardized uptake value ratios (SUVRs) were analyzed for each model across the striatal and cortical regions. Comparisons were made between single and cocktail PET scans to assess potential cross-interference of the tracers.</p> Results <p>In both PD and AD models, no statistically significant differences were observed in the SUVRs between single-tracer and cocktail PET scans in the striatum and cortex (p &gt; 0.4 for striatal comparisons, p &gt; 0.8 for cortical comparisons). Bland–Altman analysis showed no significant bias, supporting the interchangeability of SUVRs between single and cocktail PET scans.</p> Conclusions <p>This preclinical study suggests that [¹⁸F]FP-CIT and [¹⁸F]FBB PET imaging is a viable dual-target imaging approach for neurodegenerative disease evaluation. The method could streamline diagnostic workflows and improve patient convenience. Further clinical studies are warranted to validate the efficacy and safety of this approach in human populations.</p>