Evaluation of [64Cu]Cu-NOTA-PEG7-H-Tz for Pretargeted Imaging in LS174T Xenografts—Comparison to [111In]In-DOTA-PEG11-BisPy-Tz

Abstract

Pretargeted nuclear imaging for the diagnosis of various cancers is an emerging and fast developing field. The tetrazine ligation is currently considered the most promising reaction in this respect. Monoclonal antibodies are often the preferred choice as pretargeting vector due to their outstanding targeting properties. In this work, we evaluated the performance of [64Cu]Cu-NOTA-PEG7-H-Tz using a setup we previously used for [111In]In-DOTA-PEG11-BisPy-Tz, thereby allowing for comparison of the performance of these two promising pretargeting imaging agents. The evaluation included a comparison of the physicochemical properties of the compounds and their performance in an ex vivo blocking assay. Finally, [64Cu]Cu-NOTA-PEG7-H-Tz was evaluated in a pretargeted imaging study and compared to [111In]In-DOTA-PEG11-BisPy-Tz. Despite minor differences, this study indicated that both evaluated tetrazines are equally suited for pretargeted imaging.

Direct Cu-mediated aromatic 18F-labeling of highly reactive tetrazines for pretargeted bioorthogonal PET imaging

“…Open In contrast, a mean tumor-to-muscle ratio of 10 was detected which in fact is significantly higher compared to what has previously been found for the "state-of-the-art" Tz-based imaging agents [ 18 F]22 and [ 64 Cu]Cu-NOTA-PEG7-H-Tz -in a similar pretargeting setup (LS174T bearing mice, using CC49-TCO 72h prior to tracer injection, similar imaging timeframes) (Figure 4C and D). 29,61 However, [ 18 F]21 showed a 3 to 5-fold lower tumor uptake compared to those imaging agents (Figure 4E). 29,61 All tissues including tumors showed low 18 F-uptake in control animals (CC49) (tumor uptake of 0.05 ± 0.04 %ID/g).…”

“…29,61 However, [ 18 F]21 showed a 3 to 5-fold lower tumor uptake compared to those imaging agents (Figure 4E). 29,61 All tissues including tumors showed low 18 F-uptake in control animals (CC49) (tumor uptake of 0.05 ± 0.04 %ID/g). The findings from the imaging experiment were confirmed by ex vivo biodistribution data (Table S10).…”

Development of the First Aliphatic 18F-Labeled Tetrazine Suitable for Pretargeted PET Imaging – Expanding the Bioorthogonal Tool Box

“…[ 18 F]15 [ 18 F]1 [26] [ 64 Cu]Cu-NOTA-PEG7-H-Tz [33] [ 111 In]16 [33,34] PET TFA. Gradient from 100% A -> 100% B over 15minutes, back to 100% A over 4 minutes, flow rate 1.5 mL/min.…”

Direct Aromatic 18F-Labeling of Highly Reactive Tetrazines for Pretargeted Bioorthogonal PET Imaging

“…[11] In contrast, a mean tumor-to-muscle ratio of 10 was detected which in fact is significantly higher compared to what has previously been found for the "state-of-the-art" Tz-based imaging agents [ 18 F]22 and [ 64 Cu]Cu-NOTA-PEG7-H-Tzin a similar pretargeting set-up (LS174T bearing mice, using CC49-TCO 72h prior to tracer injection, similar imaging timeframes) (Figure 4C and D). [25,59] However, [ 18 F]21 showed a 3 to 5-fold lower tumor uptake compared to those imaging agents (Figure 4E). [25,59] All tissues including tumors showed low 18 F-uptake in control animals (CC49) (tumor uptake of 0.05 ± 0.04 %ID/g).…”

“…[25,59] However, [ 18 F]21 showed a 3 to 5-fold lower tumor uptake compared to those imaging agents (Figure 4E). [25,59] All tissues including tumors showed low 18 F-uptake in control animals (CC49) (tumor uptake of 0.05 ± 0.04 %ID/g). The findings from the imaging experiment were confirmed by ex vivo biodistribution data (Table S10).…”