Key result
18F-AlF-NOTA-MAL-Cys40-Exendin-4 exhibited specific binding to GLP-1R in a rat model of myocardial ischemia and reperfusion, with peak tracer uptake of 0.35 %ID/g at 8 hours post-MI/R.
Why the study?
GLP-1 and GLP-1R exert cardioprotective effects after myocardial ischemia and reperfusion, and PET provides a non-invasive method for monitoring GLP-1R expression.
Absolute Event Rate: 0.35% vs 0.06%
p-value: p=<0.05
18F-AlF-NOTA-MAL-Cys40-exendin-4 demonstrates favorable characteristics as a PET tracer for non-invasive monitoring of GLP-1R upregulation following myocardial ischemia and reperfusion.
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.
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Pan et al. (2019) studied Myocardial ischemia and reperfusion (n=36). 18F-AlF-NOTA-MAL-Cys40-Exendin-4 vs. Sham-operated was evaluated on Tracer uptake in ischemic myocardium at 8 h post-MI/R (%ID/g) (p=<0.05). 18F-AlF-NOTA-MAL-Cys40-Exendin-4 exhibited specific binding to GLP-1R in a rat model of myocardial ischemia and reperfusion, with peak tracer uptake of 0.35 %ID/g at 8 hours post-MI/R.
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