Radiosynthesis and Preclinical Evaluation of (18)F-Fluoroglycosylated Octreotate for Somatostatin Receptor Imaging

Maschauer S, Heilmann M, Waengler C, Schirrmacher R, Prante O (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Bioconjugate Chemistry American Chemical Society

Book Volume: 27

Pages Range: 2707-2714

Journal Issue: 11

DOI: 10.1021/acs.bioconjchem.6b00472

Abstract

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 (18)F-labeled octreotate analog as an alternative radiotracer for the clinically established (68)Ga-DOTATOC and (68)Ga-DOTATATE. We applied our previously developed method based on copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) to the radiosynthesis of (18)F-fluoroglycosylated TATE ([(18)F]FGlc-TATE). [(18)F]FGlc-TATE was obtained in high yields of 19-22% (non-decay-corrected, referred to [(18)F]fluoride) and in high specific activities of 32-106 GBq/?mol. [(18)F]FGlc-TATE showed high affinity to sstr expressed on AR42J cells (IC50 = 4.2 nM) with fast and high internalization, and a beneficial logD7.4 of -1.8. In AR42J tumor bearing nude mice, [(18)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 [(18)F]FGlc-TATE in the tumor which could be blocked with octreotide by >99%. Overall, [(18)F]FGlc-TATE revealed excellent in vitro and in vivo properties and is therefore a viable alternative (18)F-labeled radiopeptide for imaging somatostatin receptor-positive tumors by PET.

Authors with CRIS profile

Simone Maschauer Professur für Molekulare Bildgebung und Radiochemie Marcus Heilmann Lehrstuhl für Bioverfahrenstechnik Olaf Prante Professur für Molekulare Bildgebung und Radiochemie

Involved external institutions

University of Alberta CA Canada (CA) Ruprecht-Karls-Universität Heidelberg DE Germany (DE)

How to cite

APA:

Maschauer, S., Heilmann, M., Waengler, C., Schirrmacher, R., & Prante, O. (2016). Radiosynthesis and Preclinical Evaluation of (18)F-Fluoroglycosylated Octreotate for Somatostatin Receptor Imaging. Bioconjugate Chemistry, 27(11), 2707-2714. https://dx.doi.org/10.1021/acs.bioconjchem.6b00472

MLA:

Maschauer, Simone, et al. "Radiosynthesis and Preclinical Evaluation of (18)F-Fluoroglycosylated Octreotate for Somatostatin Receptor Imaging." Bioconjugate Chemistry 27.11 (2016): 2707-2714.

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