Improved radiosynthesis and preliminary in vivo evaluation of a 18F-labeled glycopeptide–peptoid hybrid for PET imaging of neurotensin receptor 2

Radiopharmaceuticals for imaging and endoradiotherapy of neurotensin receptor‐positive tumors

“…To date, only 1 radioligand reported selective for PET imaging of NTS2 has been reported (entry 16, Table ) . The sequence N‐Me‐Arg‐Lys‐Pro‐N‐homo‐Tyr‐Ile‐Leu‐OH was previously found to display high NTS2 affinity (2.8 nM) with 22 000‐fold selectivity over NTS1 and high stability in serum .…”

“…The sequence N‐Me‐Arg‐Lys‐Pro‐N‐homo‐Tyr‐Ile‐Leu‐OH was previously found to display high NTS2 affinity (2.8 nM) with 22 000‐fold selectivity over NTS1 and high stability in serum . Therefore, the same sequence was elongated at the N‐terminus by propargyl glycine (Pra) for radiolabeling with fluorine‐18 using CuAAC and 2‐deoxy‐2‐[ 18 F]fluoroglucosyl azide . In vitro rat brain autoradiography confirmed the high selectivity for NTS2 of the 18 F‐labeled glycopeptide.…”

18F- and 68Ga-Labeled Neurotensin Peptides for PET Imaging of Neurotensin Receptor 1

“…The copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) of deacetylated 18 an additional reaction step with per-acetylated glucopyranosyl azide was performed as described recently for the radiosynthesis of an 18 F-labeled NTS-2-radioligand, 32 to completely scavenge the alkyne precursor 13. Following this strategy, the amount of 13 as an impurity in the fraction of the final radiopeptide product was reduced to 5-10 nmol, leading to an acceptable specific activity of the final radiopeptide of 2-21 GBq/µmol ( GBq/µmol (Table 2).…”

“…31 So far, only one imaging study is dealing with the development of an NTS2 selective radioligand for PET imaging. 32 The shift from NTS1 to preferred NTS2 affinity was achieved by exchange of Tyr 11 to N-homo-Tyr 11 in the amino acid sequence, a strategy which was successfully demonstrated previously for a series of NTS2 subtype-selective peptides. 34 The 18 F-fluoroglycoslated NT analog displayed high affinity towards NTS2 (7 nM, NTS1/NTS2=260), however, it was fastly degraded in the blood and therefore displayed relatively low specific tumor uptake in vivo.…”

“…34 The 18 F-fluoroglycoslated NT analog displayed high affinity towards NTS2 (7 nM, NTS1/NTS2=260), however, it was fastly degraded in the blood and therefore displayed relatively low specific tumor uptake in vivo. 32 Taken together, all these published radiopeptide ligands for the neurotensin receptor do not demonstrate sufficient properties for in-vivo use, due to their fast metabolization or low tumor uptake.…”