English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

GLP-1 receptors are ideal targets for preoperative imaging of benign insulinoma and for quantifying the beta cell mass. The existing clinical tracers targeting GLP-1R are all agonists with low specific activity and very high kidney uptake. In order to solve those issues we evaluated GLP-1R agonist Ex-4 and antagonist Ex(9–39) radioiodinated at Tyr 40  side by side with [Nle 14 ,Lys 40 (Ahx-DOTA- 68 Ga)NH 2 ]Ex-4 ( 68 Ga-Ex-4) used in the clinic. The Kd, Bmax, internalization and binding kinetics of [Nle 14 , 125 I-Tyr 40 -NH 2 ]Ex-4 and [Nle 14 , 125 I-Tyr 40 -NH 2 ]Ex(9–39) were studied  in vitro  using Ins-1E cells. Biodistribution and imaging studies were performed in nude mice bearing Ins-1E xenografts.  In vitro  evaluation demonstrated high affinity binding of the [Nle 14 , 125 I-Tyr 40 -NH 2 ]Ex-4 agonist to the Ins-1E cells with fast internalization kinetics reaching a plateau after 30 min. The antagonist [Nle 14 , 125 I-Tyr 40 -NH 2 ]Ex(9–39) did not internalize and had a 4–fold higher K d  value compared to the agonist. In contrast to [Nle 14 , 125 I-Tyr 40 -NH 2 ]Ex(9–39), which showed low and transient tumor uptake, [Nle 14 , 125 I-Tyr 40 -NH 2 ]Ex-4 demonstrated excellent  in vivo  binding properties with tumor uptake identical to that of  68 Ga-Ex-4, but substantially lower kidney uptake resulting in a tumor-to-kidney ratio of 9.7 at 1 h compared to 0.3 with  68 Ga-Ex-4. Accumulation of activity in thyroid and stomach for both peptides, which was effectively blocked by irenat, confirms that  in vivo  deiodination is the mechanism behind the low kidney retention of iodinated peptides. The  124 I congener of [Nle 14 , 125 I-Tyr 40 -NH 2 ]Ex-4 demonstrated a similar favourable biodistribution profile in the PET imaging studies in contrast to the typical biodistribution pattern of [Nle 14 ,Lys 40 (Ahx-DOTA- 68 Ga)NH 2 ]Ex-4. Our results demonstrate that iodinated Ex-4 is a very promising tracer for imaging of benign insulinomas. It solves the problem of high kidney uptake of the radiometal-labelled tracers by improving the tumor-to-kidney ratio measured for [Nle 14 ,Lys 40 (Ahx-DOTA- 68 Ga)NH 2 ]Ex-4 by 32 fold.

Radioiodinated Exendin-4 Is Superior to the Radiometal-Labelled Glucagon-Like Peptide-1 Receptor Probes Overcoming Their High Kidney Uptake