Radiosynthesis and Preclinical Evaluation of F-Fluoroglycosylated Octreotate for Somatostatin Receptor Imaging.

Short synthetic octapeptide analogs derived from the native somatostatin peptides SST-14 and SST-28, namely, octreotate (TATE) or octreotide (TOC), bind with high affinity to somatostatin receptors (sstr), mainly to subtypes 2 and 5, which are expressed in high density on neuroendocrine tumors (NET). Therefore, radiolabeled TATE or TOC derivatives represent highly valuable imaging probes for NET diagnosis by positron emission tomography (PET). The aim of our study was the development of an F-labeled octreotate analog as an alternative radiotracer for the clinically established Ga-DOTATOC and Ga-DOTATATE. We applied our previously developed method based on copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) to the radiosynthesis of F-fluoroglycosylated TATE ([F]FGlc-TATE). [F]FGlc-TATE was obtained in high yields of 19-22% (non-decay-corrected, referred to [F]fluoride) and in high specific activities of 32-106 GBq/μmol. [F]FGlc-TATE showed high affinity to sstr expressed on AR42J cells (IC = 4.2 nM) with fast and high internalization, and a beneficial logD of -1.8. In AR42J tumor bearing nude mice, [F]FGlc-TATE showed high and specific tumor uptake of 5.6%ID/g at 60 min post-injection, as determined by blocking experiments using octreotide, and fast clearance from other organs, resulting in excellent tumor-to-blood ratios increasing from 9 to 17 from 30 to 60 min post-injection. Small animal PET studies revealed high uptake of [F]FGlc-TATE in the tumor which could be blocked with octreotide by >99%. Overall, [F]FGlc-TATE revealed excellent in vitro and in vivo properties and is therefore a viable alternative F-labeled radiopeptide for imaging somatostatin receptor-positive tumors by PET.