Radiosynthesis and evaluation of ¹⁸F-AmBF₃-TOC for imaging somatostatin receptor with positron emission tomography

Objectives Previously, we reported an ammonio-trifluoroborate octreotate conjugate, ¹⁸F-AmBF₃-TATE, that achieved high contrast for imaging somatostatin receptor subtype 2 (sst2r). In this study, we investigated if this strategy could be applied to the potent sst2r binder TOC as well.

Methods AmBF₃-TOC was prepared by conjugating azidoacetyl-TOC with N-propargyl-N,N-dimethylammoniomethyl-trifluoroborate via click chemistry. The binding affinity of AmBF₃-TOC to sst2r was determined by in vitro competition binding assay. ¹⁸F-labeling was performed via ¹⁸F-¹⁹F isotope exchange with ¹⁸F-fluoride, and ¹⁸F-AmBF₃-TOC was purified by solid phase extraction using a C18 Sep-Pak cartridge. PET imaging and biodistribution studies were performed in mice bearing sst2r-expressing ZR-75-1 human breast cancer xenograft.

Results AmBF₃-TOC bound sst2r with high affinity (K_i= 2.3 ± 1.3 nM). ¹⁸F-AmBF₃-TOC was obtained in 25 min in 17 ± 1 % decay-corrected radiochemical yield with 94 ± 2 % (n = 3) radiochemical purity. 88% and 63% of ¹⁸F-AmBF₃-TOC remained intact after 1 and 2 h incubation, respectively at 37 °C in mouse plasma. PET imaging and biodistribution showed that ¹⁸F-AmBF₃-TOC was excreted mainly via renal pathway. The tumor uptake of ¹⁸F-AmBF₃-TOC was 12.6 ± 3.66 %ID/g at 75 min post-injection, and the tumor-to-blood and tumor-to-muscle ratios were 10.9 ± 0.64 and 48.4 ± 0.58, respectively.

Conclusions ¹⁸F-AmBF₃-TOC retained high binding affinity to sst2r, and showed excellent pharmacokinetic properties with high tumor uptake and tumor-to-background contrast. Due to the superior radionuclidic and imaging properties of ¹⁸F, ¹⁸F-AmBF₃-TOC could have a widespread applicability than ⁶⁸Ga-DOTA-TOC for detection of sst2r-expressing neuroendocrine tumors with PET.