Improved stability of a novel fluorine-18 labeled TCO analogue for pretargeted PET imaging.

Biorthogonal pretargeted imaging using the inverse electron demand Diels Alder (IEDDA) reaction between tetrazine (Tz) and trans-cyclooctene (TCO) is one of the most attractive strategies in molecular imaging. It allows the use of short-lived radioisotopes such as fluorine-18 for imaging of long circulating vectors with improved imaging contrast and reduced radiation dose. Here we aim to develop a novel We have synthetized a new TCO-analogue containing a 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) chelator, allowing radiolabeling by chelation with aluminum fluoride (Al[ The radiotracer was obtained with a radiochemical yield (RCY) of 12.8 ± 2.8% and a radiochemical purity (RCP) of ≥95%. It also showed a promising in vivo stability with 51.9 ± 5.16% of radiotracer remaining intact after 1 h. The biodistribution in healthy mice demonstrated mixed hepatobiliary and renal clearance, with a rapid blood clearance and low uptake in other tissues. The low bone uptake indicated lack of tracer defluorination. Interestingly, a pretargeted PET imaging experiment showed a significantly increased radiotracer uptake (0.67 ± 0.16%ID/g, p < 0.001) in the tumors of mice pre-treated with CC49-tetrazine compared to the CC49 alone (0.16 ± 0.08%ID/g). [

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