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Glucagon‑like peptide‑1 (GLP‑1) and its receptor (GLP‑1R) exert cardioprotective effects after myocardial ischemia and reperfusion (MI/R) in animal models and human clinical trials. Receptor imaging with positron emission tomography (PET) provides a non‑invasive method for monitoring GLP‑1R expression. In the present study, a fluorine‑18‑labeled aluminum fluoride exendin‑4 analog [18F‑AlF conjugated with 1,4,7‑triazacyclononanetriacetic acid (NOTA)‑maleimide (MAL)‑Cys40‑exendin‑4] was synthesized and evaluated in a rat MI/R model for GLP‑1R imaging. NOTA‑MAL‑Cys40‑exendin‑4 was synthesized by coupling Cys40‑exendin‑4 with NOTA‑MAL. NOTA‑MAL‑Cys40‑exendin‑4 was then conjugated with 18F‑AlF to obtain 18F‑AlF‑NOTA‑MAL‑Cys40‑exendin‑4. The yield of 18F‑AlF‑NOTA‑MAL‑Cys40‑exendin‑4 was 18.5±3.4% (not decay corrected). The process was completed within ~30 min. In rat MI/R models, the tracer exhibited specific binding to GLP‑1R and an appropriate signal‑to‑noise ratio. At 8 h post‑MI/R, tracer uptake reached its peak [0.35±0.053% of injected dose (%ID)/g; n=6] in ischemic myocardium. Localized tracer uptake decreased 1 day (0.20±0.032 %ID/g; n=6) and 3 days (0.16±0.017 %ID/g; n=6) post‑MI/R compared with 8 h post‑MI/R, but still remained higher compared with sham‑operated groups (0.06±0.012 %ID/g; n=6). Pre‑injected unlabeled exendin‑4 effectively blocked tracer accumulation (0.09±0.041 %ID/g; n=6). In conclusion, 18F‑AlF‑NOTA‑MAL‑Cys40‑exendin‑4 demonstrated favorable characteristics for GLP‑1R imaging following MI/R. PET imaging using 18F‑AlF‑NOTA‑MAL‑Cys40‑exendin‑4 in rodent hearts after MI/R revealed a dynamic pattern of GLP‑1R upregulation.

Preliminary evaluation of 18F‑AlF‑NOTA‑MAL‑Cys40‑Exendin‑4 in rodent heart after myocardial ischemia and reperfusion